Incomplete radiofrequency ablation (iRFA) not only leaves residual tumor, but also render the residual tumor highly self-adaptable and immunosuppressive, consequently expediting residual tumor progression including relapse. To address it, radiofrequency dynamic therapy (RFDT) with identical trigger (namely radiofrequency) has been established and enabled by polyethylene glycol (PEG)-modified Fe-based single atom nanozyme (P@Fe SAZ). P@Fe SAZ can respond to radiofrequency field to produce reactive oxygen species (ROS), attaining the nanomedicine-unlocked low-temperature RFDT. Systematic experiments reveal that ROS further remodels iRFA-potentiated immunosuppressive microenvironment, e.g., expediting tumor-associated macrophages (TAMs) polarization into TAMs-M1, rejecting the intratumoral infiltrations of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). Coincidently, they have been demonstrated to stimulate dendritic cells (DCs) maturation and encourage the proliferations and infiltrations of effector T cells, consequently boosting anti-tumor immune responses and attenuating iRFA-enhanced plasticity, treatment resistance and self-adaptation of residual hepatocellular carcinoma (HCC) after iRFA. Thanks to them, such a nanomedicine-unlocked low-temperature RFDT exerts powerful actions on residual HCC model after iRFA with rapid expansion inhibition, relapse repression, survival prolongation, apoptosis promotion, etc. This low-temperature RFDT opens a window to address the iRFA-enhanced immunosuppression.

Immunotherapy emerges as a promising approach, marked by recent substantial progress in elucidating how the host immune response impacts tumor development and its sensitivity to various treatments. Immune checkpoint inhibitors have revolutionized cancer therapy by unleashing the power of the immune system to recognize and eradicate tumor cells. Among these, inhibitors targeting the programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have garnered significant attention due to their remarkable clinical efficacy across various malignancies. This review delves into the mechanisms of action, clinical applications, and emerging therapeutic strategies surrounding PD-1/PD-L1 blockade. We explore the intricate interactions between PD-1/PD-L1 and other immune checkpoints, shedding light on combinatorial approaches to enhance treatment outcomes and overcome resistance mechanisms. Furthermore, we discuss the expanding landscape of immune checkpoint inhibitors beyond PD-1/PD-L1, including novel targets such as CTLA-4, LAG-3, TIM-3, and TIGIT. Through a comprehensive analysis of preclinical and clinical studies, we highlight the promise and challenges of immune checkpoint blockade in cancer immunotherapy, paving the way for future advancements in the field.

Tumor-targeted T cells engineered for targeting and killing tumor cells have revolutionized cancer treatment, specifically in hematologic malignancies, through chimeric antigen receptor (CAR) T cell therapy. However, the migration of this success to lung cancer is challenging due to the tumor microenvironment (TME), antigen heterogeneity, and limitations of T cell infiltration. This review aims to evaluate current strategies addressing these barriers, focusing on the optimization of tumor-associated antigen (TAA) targeting, such as epidermal growth factor receptor (EGFR), mucin-1 (MUC1), and mesothelin (MSLN), which are frequently overexpressed in lung cancer and offer promising targets for CAR T-cell therapy. In this review, we discuss recent progress in CAR T cell engineering, applying enhanced costimulatory molecules, cytokine-secreting CAR T cells, and engineered modifications to improve T cell resilience in immunosuppressive environments. Additionally, this review also evaluates combination therapies of immune checkpoint inhibitors and recently published clinical trials on lung cancer with CAR T cells. We offer insights into the way to optimize CAR T cell therapy for lung cancer by analyzing antigen selection, immune evasion, and the strategies to enhance T cell persistence and tumor infiltration.

Skin cancer is a common malignant tumor that poses significant global health and economic burdens. The main clinical types include malignant melanoma and non-melanoma. Complications such as post-surgical recurrence, wound formation, or disfigurement can severely impact the patient's mental well-being. Traditional treatments such as surgery, chemotherapy, radiation therapy, and immunotherapy often face limitations. These challenges not only reduce the effectiveness of treatments but also negatively impact patients' quality of life. Phototherapy, a widely used and long-standing method in dermatology, presents a promising alternative for skin cancer treatment. Light-triggered nanomaterials further enhance the potential of phototherapy by offering advantages such as improved therapeutic precision, controlled drug release, minimal invasiveness, and reduced damage to surrounding healthy tissues. This review summarizes the application of light-triggered nanomaterials in skin cancer treatment, focusing on the principles, advantages, and design strategies of photodynamic therapy (PDT), photothermal therapy (PTT), and photoacoustic therapy (PAT). In this manuscript we have an in-depth discussion on overcoming translational barriers, including strategies to enhance light penetration, mitigate toxicity, reduce production costs, and optimize delivery systems. Additionally, we discuss the challenges associated with their clinical translation, including limited light penetration in deep tissues, potential toxicity, high production costs, and the need for advanced delivery systems.

Colorectal cancer (CRC) is a malignant epithelial tumor with high morbidity and mortality. In CRC treatment, irinotecan (CPT-11) as a chemotherapeutic drug is widely applied. However, its half-life is short, leading to large dosages and severe side effects. Red blood cells (RBCs) are biocompatible drug carriers with high capacity, avoiding premature drug degradation and achieving slow drug release. Nanoalumina (AN) is an emerging immune adjuvant that can enhance the immune response. Here, we used RBCs as carriers and absorbed AN to construct AN-CPT-11-RBCs. CPT-11 would induce tumor cell death, releasing much tumor antigen, while AN would activate immune cells to recognize newly released antigens and induce lymphocyte proliferation, enhancing the antitumor effect simultaneously. With loading amounts of 4 mg of CPT-11 and 3 mg of AN per 109 RBCs, AN-CPT-11-RBCs had similar properties to natural RBCs. In vivo, AN-CPT-11-RBCs could circulate for 9 days and stimulate the proliferation of lymphocytes in the spleen and tumor tissue, having a higher tumor growth inhibition rate of 74.01% and a lower frequency of administration. In conclusion, AN-CPT-11-RBCs attain the co-delivery of CPT-11 and AN for the synergistic treatment of CRC.

Altered histone deacetylase 6 (HDAC6) expression and function have been linked to cancer progression, positioning it as a promising therapeutic target for cancer treatment. Herein, we introduce HDAC6 inhibitors based on the tetrahydro-β-carboline scaffold, with compound 18d exhibiting the strongest HDAC6 inhibitory potency, achieving an IC50 of 1.3 nM. Compound 18d exhibited significant growth inhibitory activity against an NCI panel of 60 human cancer cell lines with a minimal cytotoxic effect on non-tumor cells. In vitro mechanistic investigations were conducted in HCT-116 colorectal cancer cells where the capability of 18d to enhance the acetylation of α-tubulin (HDAC6 substrate) rather than nuclear H3 histone (HDAC1 substrate) confirmed selective inhibition of HDAC6 subtype. Additionally, compound 18d was observed to suppress the S phase and promote accumulation in the apoptotic sub-G1 phase, potentially through increasing cleaved caspase 3 and reducing Bcl-2 levels in HCT-116 cells. A wound healing assay also elicited the ability of 18d to hinder cell migration. Notably, 18d could suppress the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, a crucial signaling pathway implicated in cancer cell proliferation, migration and apoptosis. Moreover, downregulation of the critical immune checkpoint protein programmed death-ligand 1 (PD-L1) revealed a potential role of 18d in augmenting immune response towards tumor cells. In summary, these findings highlight 18d's dual role in direct tumor growth suppression and immune system sensitization, highlighting a broader cancer therapeutic potential beyond conventional HDAC inhibition.

The intricate interaction between skeletal muscle biomechanics, the tumor microenvironment, and immunotherapy constitutes a pivotal research focus oncology. This work provides a comprehensive review of methodologies for evaluating skeletal muscle biomechanics, including handheld dynamometry, advanced imaging techniques, electrical impedance myography, elastography, and single-fiber experiments to assess muscle quality and performance. Furthermore, it elucidates the mechanisms, applications, and limitations of various immunotherapy modalities, including immune checkpoint inhibitors, adoptive cell therapy, cancer vaccines, and combined chemoimmunotherapy, while examining their effects on skeletal muscle function and systemic immune responses. Key findings indicate that although immunotherapy is effective in augmenting antitumor immunity, it frequently induces muscle-related adverse effects such as weakness, fatigue, or damage, primarily mediated by cytokine release and immune activation. This work underscores the significance of immune niches within the tumor microenvironment in influencing treatment outcomes and proposes strategies to optimize therapy through personalized regimens and combinatorial approaches. This review highlights the need for further research on the formation of immune niches and interactions muscle-tumor. Our work is crucial for advancing the efficacy of immunotherapy, reducing adverse effects, and ultimately improving survival rates and quality of life of patients with cancer.

Cancer immunotherapy has transformed the treatment landscape, introducing new strategies to fight various types of cancer. This review examines the important role of vaccines in cancer therapy, focusing on recent advancements such as dendritic cell vaccines, mRNA vaccines, and viral vector-based approaches. The relationship between cancer and the immune system highlights the importance of vaccines as therapeutic tools. The discussion covers tumor cell and dendritic cell vaccines, protein/peptide vaccines, and nucleic acid vaccines (including DNA, RNA, or viral vector-based), with a focus on their effectiveness and underlying mechanisms. Combination therapies that pair vaccines with immune checkpoint inhibitors, TIL therapy, and TCR/CAR-T cell therapy show promising potential, boosting antitumor responses. Additionally, the review explores the regulatory functions of microRNAs (miRNAs) in cancer development and suppression, featuring miR-21, miR-155, the let-7 family, and the miR-200 family, among others. These miRNAs influence various pathways, such as PI3K/AKT, NF-κB, and EMT regulation, providing insights into biomarker-driven therapeutic strategies. Overall, this work offers a thorough overview of vaccines in oncology and the integrative role of miRNAs, setting the stage for the next generation of cancer immunotherapies.

Cancer is a multifaceted disease characterized by uncontrollable cell growth. To date, various therapies are employed including conventional chemotherapy, surgery, radiotherapy, and immunotherapies. However, these approaches still present significant limitations. Interestingly, macrophage membranes utilize their innate antigen recognition affinity to facilitate targeted localization to tumor sites with high specificity. As a result, they display distinct characteristics such as avoiding premature leakage, tumor targeting ability, immune evasion, immune system activation, tumor-infiltrating ability, improved cell endocytosis and release payload in tumor-microenvironment. In this paper, the recent advances in macrophage-membrane-encapsulated nanotherapeutics for targeted cancer therapy are presented. We begin by introducing macrophage membrane-encapsulated nanotherapeutics preparation and characterization, followed by cancer immunotherapy such as macrophage polarization, T-cell infiltration, macrophage membrane modification, immunization, and inducing immunological cell death. Lastly, a future perspective is proposed to highlight the limitations of macrophage membrane-encapsulated nanotherapeutics and the possible resolutions toward the clinical transformation of currently developed biomimetic chemotherapies. We believe this review may be beneficial for improving the deep research of macrophage membrane-encapsulated nanotherapeutics for targeted cancer therapy.

Bacterial outer membrane vesicles (OMVs), naturally released by Gram-negative bacteria, are a type of lipid bilayer nanoparticles containing many components found within the parent bacterium. Despite OMVs were first considered mere by-products of bacterial growth, recent studies have shown them as a highly adaptable platform for tumor vaccine. Here, we first demonstrate the biogenesis of OMVs, then review the strong immunogenicity of OMVs as an immune adjuvant in tumor vaccine and its excellent vaccine delivery capability, and finally discuss OMVs' engineering potentials through summarizing recent scientific advancements in genetic engineering, chemical modification, and nanotechnology. We also point out the clinical trials and future challenges of OMV-based vaccine. Overall, this review offers valuable insights into cancer immunotherapy, providing a roadmap for leveraging OMVs as a versatile platform for next-generation cancer vaccines.

Cancer is still a major health concern worldwide, requiring ongoing improvements in methods of diagnosis and treatment. During the past decade, smart biosensors have become essential instruments in cancer theranostics, improving diagnosis accuracy, tracking treatment efficacy, and customizing patient care. This review thoroughly investigates how smart biosensors have revolutionized the field of cancer. The potential of major technical advancements, such as wearable technology, microfluidic platforms, and sensors based on nanomaterials to identify cancer biomarkers with high sensitivity and specificity is investigated. A detailed discussion is held regarding clinical applications that include early diagnosis, real-time monitoring of therapy responses, and support for personalized medicine techniques. Future directions targeted at optimizing the therapeutic utility of smart biosensors in oncology are also examined, along with issues pertaining to regulatory routes and clinical translation hurdles. This study highlights the potential of smart biosensors to transform cancer treatment, bringing in a new era of precision medicine and better patient outcomes by combining insights from multiple viewpoints.

Immunotherapy has become one of the innovative treatments in malignancy as it activates the immune system to find and eliminate malignant cells. The tumor immunology interface has become increasingly intricate, making the identification of new immune targets and signalling pathways on which to base improved therapeutic strategies an ongoing process. This review, we goal to clarify the contacts between cancer and immune system with a focus on immune surveillance as well as immune evasion mechanisms. Comprehensive immunotherapeutic therapies are overviewed with ICI (CTLA-4, PD-1, PD-L1), CAR-T cell therapy, and cancer vaccines whereas, advanced therapies targeting new immune checkpoints are also elucidated including TIM-3, LAG-3, and TIGIT. The JAK/STAT, MAPK and PI3K-AKT-mTOR pathways are reviewed with regards to cancer progression and immunotherapeutic resistance. The dysregulation of these pathways gives hope for the identification of fresh targets for therapy. Genomics, proteomics, immunopeptidomics, single cell mass spectrometry, CRISPR-based functional genomics and bioinformatics are described as essential for immune target identification and for mapping of cancer relevant signaling pathways. This review also considers some emerging issues in the subject area like the tumor heterogeneity, immune-related adverse events (irAEs), and personalized treatment. These barriers are described to facilitate the understanding of ways to overcome them and increase the efficacy of immunotherapies through combination therapies. This means that by developing new knowledge of immunological targets and pathways, immunoprecision medicine for cancer could greatly enhance outcomes.

Chito-oligosaccharide (COS) is a low molecular weight polymer obtained by degrading chitosan through special enzymatic technology, with good water solubility and high biological activity. It is also the only positively charged cationic basic amino oligosaccharide in nature. Studies have confirmed that COS has antitumour effect, but research on its effect on pancreatic cancer (PC) remains limited and unclear. This study aimed to explore the effects of COS on PC cells (PANC-1 and MIAPaCa-2).

We used different concentrations of COS to treat PC cells and conducted Cell Counting Kit-8, wound-healing, and transwell assays to evaluate the proliferation, invasion, and migration ability of PC cells, respectively. Western blot was conducted to assess the expression levels of epithelial-mesenchymal transition (EMT) related markers.

The proliferation, invasion, and migration ability of PC cells (PANC-1 and MIAPaCa-2) gradually decreased in a manner dependent on COS concentration. COS at 10 mg/mL exerted the strongest inhibitory effect on the two PC cell lines. At 10 mg/mL, the proliferative activity was 60.61% ± 5.25% and 64.02% ± 4.96%, respectively; the invasive ability was (18.67 ± 4.416) and (31.33 ± 3.162), respectively; and the cell-migration ability was 26.83% ± 0.442% and 17.66% ± 0.647%, respectively. The expression levels of N-cadherin and vimentin were significantly downregulated in PANC-1 cells (0.198 ± 0.047 and 0.225 ± 0.038, respectively) and MIAPaCa-2 cells (0.214 ± 0.094 and 0.214 ± 0.094, respectively) at 10 mg/mL, respectively. Conversely, E-cadherin was upregulated (0.460 ± 0.037 and 0.491 ± 0.047, respectively). Compared with control group, the differences were statistically significant.

The upregulation of E-cadherin and the downregulation of vimentin and N-cadherin suggested that the specific mechanism of COS in PC may be related to EMT. This study provided a new direction for PC treatment.

Cancer immunotherapy leverages the immune system to combat cancer and has shown promise for many patients. However, its effectiveness is often hampered by an immunosuppressive tumor microenvironment and the low immunogenicity of tumor cells. In this study, we developed an in situ cancer vaccine that integrates chemotherapy and immunotherapy in a single platform. We synthesized two amphiphilic polymers with poly-albumin-binding domains (PABD) that can target the lymph nodes, PABD-PGEA and PABD-PGED. Compared with previous albumin-hijacking strategies utilizing the same albumin-binding domains, PABD-PGEA exhibited approximately six times greater lymph node-targeting ability, demonstrating enhanced antigen-capturing capability. We loaded PABD-PGEA with doxorubicin (DOX), a drug known to induce immunogenic cell death (ICD) in tumor cells, to form DOX@PABD-PGEA nanomicelles. DOX@PABD-PGEA inhibited tumor growth and extended the survival of mice with B16F10 melanoma through chemotherapy and immunotherapy. Notably, DOX@PABD-PGEA prevented tumor recurrence post-surgery by promoting efficient antigen presentation and reversing immunosuppression in the tumor microenvironment. Our findings suggest that DOX@PABD-PGEA, as an antigen-capturing nanoparticle, provides a safe and effective platform for in situ cancer vaccines and improves cancer immunotherapy.

This study aims to investigate the adverse effects of immune checkpoint inhibitors (ICIs) on the female and male reproductive systems. In the FDA Adverse Event Reporting System (FAERS) database, adverse reactions under the "Reproductive system and breast disorders" category in the System Organ Classes were included, covering a period from January 1, 2015, to June 30, 2023. We identified 133,512 patients treated with ICIs. Immune checkpoint inhibitor-related reproductive adverse effects (irRAEs) were reported in 568 (0.43%) patients. Spermatogenesis abnormality (ROR025 = 7.91) had the highest signal strength associated with ICI use in males. Genital tract fistula was the only significant irRAE (ROR025 = 2.72) in females. PD-1 inhibitors pose greater risk than CTLA-4 inhibitors (OR = 1.65 [1.05-2.79], p = 0.045). Gynecologic cancers in females (OR = 3.77 [2.82-4.99], p < 0.0001) and urogenital cancers in males (OR = 1.56 [1.17-2.06], p = 0.0018) carried the highest risk compared to other cancers. Additional targeted drugs (OR = 2.32 [1.76-3.02], p < 0.0001), particularly lenvatinib (OR = 3.50 [2.48-4.94], p < 0.0001) and cabozantinib (OR = 3.71 [1.96-7.03], p < 0.0001) significantly increased the risk for females. Additional use of chemotherapy drugs was associated with a significant reduction in the risk for males (OR = 0.65 [0.42-0.96], p = 0.042) except for doxorubicin (OR = 2.58 [1.22-5.47], p = 0.013) and cyclophosphamide (OR = 2.36 [1.05-5.29], p = 0.038). This study demonstrates that ICIs could potentially lead to a wide range of adverse effects in the reproductive system in both males and females.

The epidermal growth factor (EGF) receptor is commonly targeted in cancer therapy because it is overexpressed in many malignant cells. However, a general problem is to couple the targeting moieties and the drug molecules in a way that results in a homogeneous product. Here, we overcome this issue by engineering a variant of EGF with a single conjugation site for coupling virtually any payload. The recombinant EGF variant K-EGFRR was expressed in E. coli Rosetta with a 4-6 mg/L yield. To confirm the accessibility of the introduced functional group, the ligand was equipped with a sulfo-cyanine dye with a loading of 0.65 dye per ligand, which enables tracking in vitro. The kinetics and affinity of ligand-receptor interaction were evaluated by enzyme-linked immunosorbent assay and surface plasmon resonance. The affinity of K-EGFRR was slightly higher when compared to the wild-type EGF (K D: 5.9 vs. 7.3 nM). Moreover, the ligand-receptor interaction and uptake in a cellular context were evaluated by flow cytometry and quantitative high-content imaging. Importantly, by attaching heterobifunctional polyethylene glycol linkers, we allowed orthogonal click-conjugation of the ligand to any payload of choice, making K-EGFRR an ideal candidate for targeted drug delivery.

Nanozymes exhibit significant potential in medical theranostics, environmental protection, energy development, and biopharmaceuticals due to their exceptional catalytic performance. Compared with natural enzymes, nanozymes have the advantages of simple preparation and purification, convenient production and low cost. Therefore, it is very important to prepare nanozymes quickly and efficiently, which not only helps to expand their application scope, but also can further exert their great potential in various fields. Metal-organic frameworks (MOF) materials serve as versatile substrates for constructing nanozymes, offering unique advantages like adjustable structure, high specific surface area, and porous channels. MOF coordination nodes constructed from metal ions or metal clusters have unique properties that can be leveraged to tailor nanozyme characteristics for different applications. This review describes and analyzes recent methods for constructing nanozymes using MOF materials, and explores their application prospects in biomedicine. By expounding the preparation techniques and biomedical applications of nanozymes, this review aims to inspire researchers to develop innovative nanozyme materials and explore new application directions.

The JAK2V617F mutation plays a crucial part in the pathogenesis of myeloproliferative neoplasms (MPN), which includes polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) leading to aberrant proliferation and survival of hematopoietic cells. Alongside the challenges of drug resistance and side effects, identifying novel compounds that selectively target JAK2V617F could provide more effective and safer therapeutic options for patients with MPNs.

We employed computational approaches like high-throughput virtual screening, molecular dynamics simulations (MDS), and binding free energy calculations to identify inhibitors targeting wild and mutant JAK2 kinases. JAK2V617F positive HEL, wild type JAK2 positive TF-1, and non-cancerous Vero cells were used for in vitro validations.

SBLJ23 emerged as a top candidate inhibitor with specificity for JAK2V617F. Protein-ligand interaction studies and MDS revealed stable interactions and binding of SBLJ23 over the simulation period, with Root Mean Square Deviation (RMSD) indicating consistent binding after 1t15ns. SBLJ23 displayed a half maximal inhibitory concentration (IC50) value of 522.4 nM against the JAK2 enzyme. The compound exhibited inhibition of cell proliferation in HEL and TF-1 cells, with half maximal cell growth inhibitory concentration (GI50) values of 2.51 and 15.87 µM, respectively. Moreover, SBLJ23 induced G2/M cell cycle arrest in HEL cells to facilitate apoptosis in these cell lines. The compound significantly reduced the percentage of phospho JAK2 and phospho STAT3 in HEL cells.

High binding affinity, stable interaction profile, favorable binding free energy, and in vitro validations claim SBLJ23 as a potential lead compound against JAK2V617F and suggest further development and optimization towards clinical application in managing myeloproliferative neoplasms.

Human papillomavirus (HPV) contributes to a high global incidence of sexually transmitted infections, predominantly associated with cervical cancer, as well as head and neck, penile, anal, vaginal, and vulvar cancers. Despite efforts through improved screening and HPV vaccination campaigns, challenges persist, influencing the frequency of HPV-related malignancies. Collaborative scientific endeavors strive to pioneer groundbreaking approaches, aiming to alleviate the adverse consequences of HPV-related malignancies on individuals and communities. The present review is focused on exhaustively covering HPV-associated cancers, particularly cervical cancer. This study highlights the initiation, progression, immune invasion, and treatment strategies of HPV-associated cancers. The role of viral oncoproteins E6 and E7 responsible for immune evasion and subsequent latent infection is also elaborated. The article also sheds light on the pivotal role of HPV vaccination in averting high-risk HPV infections and associated cancers. The scope of this review encompasses HPV-associated cancer epidemiology, regional disparities, and the distinctive challenges faced in the context of India. This will be a value addition to the knowledge repertoire beneficial for creating awareness and designing health policies.

Doxorubicin + cisplatin and paclitaxel + carboplatin are standard chemotherapy regimens for endometrial cancer. The development of PD-1 and PDL-1 antibody drugs has led to the use of these agents for endometrial cancer in other countries. The KEYNOTE-775 trial for advanced or recurrent endometrial cancer demonstrated the benefits of pembrolizumab and lenvatinib combination therapy, and the results of this trial led to the approval of its coverage for recurrent cancer by the Japanese health insurance system. Currently, treatment with immune checkpoint inhibitors is transitioning from second-line to first-line therapy. In a global randomized phase III study, the drugs dostarlimab, durvalumab, and atezolizumab, which are not yet approved in Japan, showed better results in the study arms than in the control arm. Additionally, biomarkers have been developed for endometrial cancer, enabling gynecologists to pursue treatment options based on the biomarkers detected for better treatment outcomes. In this article, we review the clinical trials of immune checkpoint inhibitors for advanced or recurrent endometrial cancer.

In classical photodynamic therapy, tumor cells are killed by the cytotoxic species via type-I/II photochemical reactions, seriously limited by the external photoexcitation and hypoxia. Herein, the electron transfer mechanism between fluorophores and peroxalate-H2O2 reaction is investigated and the singlet/triplet electron exchange is utilized to achieve long-persistent chemiluminescence imaging and synergistic type-I/II/III photodynamic therapy. As a proof-of-concept, the photosensitizers of carbon nanodots (CDs)-loaded chlorin e6 (CDs-Ce6) are designed and integrated with the peroxalate molecules, and the as-prepare polymer carbon nanodots (p-CDs) exhibit novel tumor microenvironment (TME)-responsive long-persistent near-infrared CL and photochemical reactions, evoking the in vivo imaging and synergistic dynamic therapy in tumor tissue. Mechanistically, the excess reactive oxygen species in TME can trigger the chemically initiated singlet/triplet electron exchange between the hydrophobic CDs-Ce6 and peroxalate-derived 1,2-dioxetanes and thus the excess excited singlet/triplet electron of the CDs-Ce6 can ensure the long-persistent near-infrared CL, type I/II photochemical production of hydroxyl radicals, superoxide radical and singlet oxygen, and type III photochemical damage of maladjusted biomacromolecules, enabling the long-persistent near-infrared biological imaging and enhanced cancer therapy. These results shed a new sight into the energy transfer mechanism in chemiluminescence and pave a new sight into the architecture of multifunctional theragnostic nanoplatforms.

Light-based immunotherapy uses specific wavelengths of light to activate or modulate immune responses. It primarily employs two mechanisms: direct activation of immune cells and indirect modulation of the tumor microenvironment (TME). Several light-based technologies are under investigation or clinical use in immunotherapy, including photodynamic immunotherapy (PDIT) and photothermal therapy (PTT). Optogenetic tools have the potential to precisely control T-cell receptor activation, cytokine release, or the activity of other immune effector cells. Light-based technologies present innovative opportunities within the realm of immunotherapy. The ability to precisely regulate immune cell activation via optogenetics, alongside the improved targeting of cancer cells through photoimmunotherapy, signifies a transformative shift in our strategies for immune modulation. Although many of these technologies remain in the experimental stage for various applications, initial findings are encouraging, especially concerning cancer treatment and immune modulation. Continued research and clinical trials are essential to fully harness the capabilities of light technology in the context of immune cell therapy.

Gene editing techniques have emerged as powerful tools in biomedical research, offering precise manipulation of genetic material with the potential to revolutionize cancer treatment strategies. This review provides a comprehensive overview of the current landscape of gene editing technologies, including CRISPR-Cas systems, base editing, prime editing, and synthetic gene circuits, highlighting their applications and potential in cancer therapy. It discusses the mechanisms, advantages, and limitations of each gene editing approach, emphasizing their transformative impact on targeting oncogenes, tumor suppressor genes, and drug resistance mechanisms in various cancer types. The review delves into population-level interventions and precision prevention strategies enabled by gene editing technologies, including gene drives, synthetic gene circuits, and precision prevention tools, for controlling cancer-causing genes, targeting pre-cancerous lesions, and implementing personalized preventive measures. Ethical considerations, regulatory challenges, and future directions in gene editing research for cancer treatment are also addressed. This review highlights how gene editing could revolutionize precision medicine by enhancing patient care and advancing cancer treatments with targeted, personalized methods. For these benefits to be fully realized, collaboration among researchers, doctors, regulators, and patient advocates is crucial in fighting cancer and meeting clinical needs.

Cancer remains a leading cause of morbidity and mortality worldwide. Traditional treatments like chemotherapy and radiation often result in significant side effects and varied patient outcomes. Immunotherapy has emerged as a promising alternative, harnessing the immune system to target cancer cells. However, the complexity of immune responses and tumor heterogeneity challenges its effectiveness.

This mini-narrative review explores the role of artificial intelligence [AI] in enhancing the efficacy of cancer immunotherapy, predicting patient responses, and discovering novel therapeutic targets.

A comprehensive review of the literature was conducted, focusing on studies published between 2010 and 2024 that examined the application of AI in cancer immunotherapy. Databases such as PubMed, Google Scholar, and Web of Science were utilized, and articles were selected based on relevance to the topic.

AI has significantly contributed to identifying biomarkers that predict immunotherapy efficacy by analyzing genomic, transcriptomic, and proteomic data. It also optimizes combination therapies by predicting the most effective treatment protocols. AI-driven predictive models help assess patient response to immunotherapy, guiding clinical decision-making and minimizing side effects. Additionally, AI facilitates the discovery of novel therapeutic targets, such as neoantigens, enabling the development of personalized immunotherapies.

AI holds immense potential in transforming cancer immunotherapy. However, challenges related to data privacy, algorithm transparency, and clinical integration must be addressed. Overcoming these hurdles will likely make AI a central component of future cancer immunotherapy, offering more personalized and effective treatments.

Angiosarcomas are a type of soft-tissue sarcoma characterized by aggressive malignant tumors originating from endothelial cells of blood vessels or lymphatic vessels. Limited studies have been done to explore the molecular pathophysiology of the disease, with rather limited studies involving transcriptomic analyzes. This study was undertaken to identify the shared molecular signatures and gene modules associated with angiosarcomas of various origin. Transcriptomic data analysis of publicly available data was done followed by WGCNA to identify shared signature gene modules. The Maximal Clique Centrality algorithm was applied to gene modules, and unclustered network analysis was conducted on differentially expressed genes to identify true hub genes. The expression of candidate genes in various cancer types was analyzed using GEPIA. WGCNA analysis identified five significant modules, with the most enriched module being associated with angiogenesis and cell junction regulators. The intersection of true hub genes from MCC analysis of WGCNA modules and high-degree nodes from an unclustered network revealed eight consistently overexpressed genes in all angiosarcoma samples.Among the eight enriched genes, CHRNA5 and CTLA4, are exclusively overexpressed in angiosarcoma and not in other cancers of the same tissue origin, with significant drug-protein interactions suggesting their potential as therapeutic targets.

RAF kinases, particularly the BRAF isoform, play a crucial role in the MAPK/ERK signaling pathway, regulating key cellular processes such as proliferation, differentiation, and survival. Dysregulation of this pathway often caused by mutations in the BRAF gene or alterations in upstream regulators like Ras and receptor tyrosine kinases contributes significantly to cancer development. Mutations, such as BRAF-V600E, are present in a variety of malignancies, with the highest prevalence in melanoma. Targeted therapies against RAF kinases have achieved substantial success, especially in BRAF-V600E-mutant melanomas, where inhibitors like vemurafenib and dabrafenib have demonstrated remarkable efficacy, leading to improved patient outcomes. These inhibitors have also shown clinical benefits in cancers such as thyroid and colorectal carcinoma, although to a lesser extent. Despite these successes, therapeutic resistance remains a major hurdle. Resistance mechanisms, including RAF dimerization, feedback reactivation of the MAPK pathway, and paradoxical activation of ERK signaling, often lead to diminished efficacy over time, resulting in disease progression or even secondary malignancies. In response, current research is focusing on novel therapeutic strategies, including combination therapies that target multiple components of the pathway simultaneously, such as MEK inhibitors used in tandem with RAF inhibitors. Additionally, next-generation RAF inhibitors are being developed to address resistance and enhance therapeutic specificity. This review discusses the clinical advancements in RAF-targeted therapies, with a focus on ongoing efforts to overcome therapeutic resistance and enhance outcomes for cancer patients. It also underscores the persistent challenges in effectively targeting RAF kinase in oncology.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality globally. Recent advancements in targeted therapies have improved outcomes for advanced HCC, yet therapeutic options remain limited. The CARES-310 trial demonstrated that camrelizumab plus rivoceranib significantly improves survival compared to sorafenib for advanced HCC.

This study aimed to evaluate the cost-effectiveness of camrelizumab plus rivoceranib as a first-line treatment for unresectable HCC from the Chinese health system perspective.

The cost-effectiveness analysis.

A partitioned survival model was constructed to estimate clinical and economic outcomes for patients with unresectable or metastatic HCC. The model included three health states: progression-free, progression disease, and death. The hypothetical cohort consisted of patients aged ⩾18 with HCC who had not received systemic therapy, reflecting the CARES-310 trial. Clinical data were derived from the CARES-310 trial and extrapolated using standard parameter distributions. Direct medical costs and utilities were sourced from the CARES-310 trial and published literature.

The 10-year cost of camrelizumab plus rivoceranib was higher than sorafenib (USD 28,148.01 vs USD 20,997.86). Camrelizumab plus rivoceranib yielded an additional 0.26 quality-adjusted life-years (QALYs) with an incremental cost of USD 7150.15, resulting in an incremental cost-effectiveness ratio of USD 27,633.75/QALY. Sensitivity analyses confirmed the robustness of the base-case results.

Camrelizumab plus rivoceranib is likely a cost-effective first-line treatment for unresectable HCC from a Chinese health system perspective. This study highlights the need for additional real-world data to validate these findings and guide clinical decision-making for HCC.

The American Society of Clinical Oncology (ASCO) updated the guidelines for the treatment of advanced gastroesophageal (GE) cancer in 2023, signifying a major shift towards targeted therapeutics and precision medicine. This article serves as an imaging-based review of recent developments in the care of patients with GE cancer. We cover the epidemiology, the developing treatment paradigms, and the imaging assessment of GE malignancy. In addition, this review aims to familiarize radiologists with the unique adverse effects pertaining to therapeutics, surgeries, radiation therapies, and associated imaging corollaries. A case-based approach will be used to both explore the efficacy of modern treatments and demonstrate their adverse effects, such as chemotherapy-associated pneumonitis, radiation esophagitis, and anastomotic failure. With this comprehensive exploration of gastroesophageal cancer, radiologists will be equipped with the essential tools to inform the treatment decisions made by medical oncologists, radiation oncologists, and surgical oncologists in the new era of precision medicine.

Adavosertib (AZD1775) is a small-molecule Wee1 inhibitor. Durvalumab is a PD-L1 inhibitor.

The safety, tolerability, pharmacokinetics, and preliminary antitumor activity of adavosertib plus durvalumab were evaluated in patients with refractory solid tumors to define the maximum tolerated dose (MTD) and recommended phase II dose (RP2D).

This phase 1, non-randomized, open-label study determined MTD/RP2D using dose-escalation cohorts. Eligible patients had histologically confirmed tumors refractory to standard therapy or for which no standard of care existed.

A total of 55 patients received adavosertib with durvalumab. Overall, 3/52 evaluable patients experienced dose-limiting toxicities (DLTs; two grade 3 nausea, one grade 3 diarrhea that did not respond to care within 48 h). The most frequent (in > 5% of patients) treatment-emergent grade ≥ 3 toxicities were fatigue, diarrhea, nausea, anemia, and abdominal pain. MTD for twice-daily (bid) adavosertib dosing was oral adavosertib 150 mg bid (3 days on/4 days off; treatment days 15-17 and 22-24 of a 28-day cycle) with intravenous durvalumab 1500 mg four times a week (Q4W), which was also the RP2D. MTD for once-daily (qd) adavosertib dosing was oral adavosertib 300 mg qd (5 days on/2 days off; treatment days 15-19 and 22-26 of a 28-day cycle) with intravenous durvalumab 1500 mg Q4W.

This study defined the MTD/RP2D of adavosertib plus durvalumab in patients with advanced solid tumors. The safety profile of adavosertib with durvalumab was consistent with the known safety data of each agent. Findings provide preliminary evidence of limited antitumor activity of adavosertib plus durvalumab.

ClinicalTrials.gov, NCT02617277 (registration: 30 November 2015).

Cancer immunotherapy has shifted the paradigm for clinical cancer treatment in the past decade, especially with the success of checkpoint blockades and chimeric antigen receptor (CAR)-T cell therapy. However, the low patient response rate to checkpoint blockades, poor efficacy of CAR-T cell therapy against solid tumors, and severe side effects in both have limited the utility of cancer immunotherapy. These issues motivate the development of new immunotherapies that can induce persistent cytotoxic T lymphocyte response with minimal side effects. This often requires the targeted modulation of specific types of immune cells (e.g., dendritic cells and T cells) in lymphatic tissues or cancerous tissues, which is inevitably challenging. Immune cell homing materials, though, enable in situ recruitment and modulation of immune cells for the orchestration of systemic immune responses and overall antitumor efficacy. Here we introduce the design, synthesis, characterization, and immune analysis of dendritic cell-homing macroporous hydrogels for the development of cancer immunotherapy.

Oral cancer is a major global health concern, with high incidence and mortality rates, especially in high-risk populations. Early diagnosis remains a challenge, and current treatments, such as surgery, radiation, and chemotherapy, have limited effectiveness, particularly in advanced stages. Recent advances in targeted therapies and immunotherapy offer promising alternatives, providing more precise and personalized treatment options. Targeted therapies, such as epidermal growth factor receptor inhibitors, aim to disrupt specific molecular pathways in tumor growth, while immunotherapies, including immune checkpoint inhibitors and chimeric antigen receptor-T cell therapy, enhance the body's immune response to fight cancer. Combination therapies, integrating both targeted and immune strategies, are being explored to overcome the limitations of single-agent treatments. This review highlights the current strategies in the prevention and treatment of oral cancer, discusses emerging therapies, explores future research directions, focusing on optimizing existing treatments, identifying new biomarkers, and developing innovative therapeutic approaches. The potential of personalized medicine and combination therapies offers new hope for improving survival rates and quality of life for oral cancer patients.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. Metastatic colorectal cancer (mCRC) continues to present significant challenges, particularly in patients with proficient mismatch repair/microsatellite stable (pMMR/MSS) tumors. This narrative review aims to provide recent developments in immunotherapy for CRC treatment, focusing on its efficacy and challenges.

This review discussed the various immunotherapeutic strategies for CRC treatment, including immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1, combination therapies involving ICIs with other modalities, chimeric antigen receptor T-cell (CAR-T) cell therapy, and cancer vaccines. The role of the tumor microenvironment and immune evasion mechanisms was also explored to understand their impact on the effectiveness of these therapies.

This review provides a comprehensive update of recent advancements in immunotherapy for CRC, highlighting the potential of various immunotherapeutic approaches, including immune checkpoint inhibitors, combination therapies, CAR-T therapy, and vaccination strategies. The results of checkpoint inhibitors, particularly in patients with MSI-H/dMMR tumors, which have significant improvements in survival rates have been observed. Furthermore, this review also addresses the challenges faced in treating pMMR/MSS CRC, which remains resistant to immunotherapy.

Immunotherapy plays a significant role in the treatment of CRC, particularly in patients with MSI-H/dMMR tumors. However, many challenges remain, especially in treating pMMR/MSS CRC. This review discussed the need for further research into combination therapies, biomarker development, CAR-T cell therapy, and a deeper understanding of immune evasion mechanisms for CRC treatment.

Immunology-based therapies are emerging as an effective cancer treatment, using the body's immune system to target tumors. Immune checkpoints, which regulate immune responses to prevent tissue damage and autoimmunity, are often exploited by cancer cells to avoid destruction. The discovery of checkpoint proteins like PD-1/PD-L1 and CTLA-4 was pivotal in developing cancer immunotherapy. Immune checkpoint inhibitors (ICIs) have shown great success, with FDA-approved drugs like PD-1 inhibitors (Nivolumab, Pembrolizumab, Cemiplimab), PD-L1 inhibitors (Atezolizumab, Durvalumab, Avelumab), and CTLA-4 inhibitors (Ipilimumab, Tremelimumab), alongside LAG-3 inhibitor Relatlimab. Research continues on new checkpoints like TIM-3, VISTA, B7-H3, BTLA, and TIGIT. Biomarkers like PDL-1 expression, tumor mutation burden, interferon-γ presence, microbiome composition, and extracellular matrix characteristics play a crucial role in predicting responses to immunotherapy with checkpoint inhibitors. Despite their effectiveness, not all patients experience the same level of benefit, and organ-specific immune-related adverse events (irAEs) such as rash or itching, colitis, diarrhea, hyperthyroidism, and hypothyroidism may occur. Given the rapid advancements in this field and the variability in patient outcomes, there is an urgent need for a comprehensive review that consolidates the latest findings on immune checkpoint inhibitors, covering their clinical status, biomarkers, resistance mechanisms, strategies to overcome resistance, and associated adverse effects. This review aims to fill this gap by providing an analysis of the current clinical status of ICIs, emerging biomarkers, mechanisms of resistance, strategies to enhance therapeutic efficacy, and assessment of adverse effects. This review is crucial to furthering our understanding of ICIs and optimizing their application in cancer therapy.

Oral nanomedicines present a preferable avenue for cancer immunotherapy, but their efficacy is limited by gastrointestinal absorption challenges, tumor physiopathologic barriers, and immune evasion mechanisms. Here, we present an approach that combines an oral transcytotic doxorubicin (DOX) nanomedicine with the histone demethylase inhibitor 5-carboxy-8-hydroxyquinoline (IOX1), thereby enabling synergistic chemoimmunotherapy. We demonstrate that IOX1 significantly augments the transcytosis capabilities of DOX-loaded poly(2-(N-oxide-N,N-diethylamino)ethylmethacrylate)-poly(ε-caprolactone) micelles (OPDOX), promoting their transcellular transport across various cellular barriers (villus, endothelial, and tumor cells), thus improving oral adsorption, vascular extravasation, and tumor penetration. Furthermore, IOX1 sensitizes chemotherapy to potentiate DOX-induced immunogenic cell death and downregulates programmed cell death-ligand 1 to disrupt the immune checkpoint mechanism, synergistically boosting robust antitumor immune responses. Consequently, orally administered OPDOX in combination with IOX1 efficiently inhibits CT26 tumor growth, highlighting the significant potential for enhancing the efficacy of oral nanomedicines in cancer chemoimmunotherapy.

To establish a pragmatic and effective predictive model for monitoring the recovery of radiation enteritis (RE) in cervical cancer patients undergoing concurrent chemoradiotherapy (CCRT).

This study included 105 cervical cancer patients undergoing CCRT. We assessed baseline clinicopathologic characteristics, evaluated the effects of CCRT on circulating immune cells, tumor biomarkers, and inflammatory cytokines, and developed a predictive scoring system, the Immune-Tumor-Score (ITS), using the LASSO-Cox regression model. The model performance of LASSO-Cox and nomogram was compared via ROC curve and calibration curve.

The median age of the patients was 55 years, with 53.3% having a normal BMI and 46.7% having positive lymph nodes. Post-CCRT, significant decreases were observed in lymphocyte counts, T-cell subpopulations, and tumor markers (CA125, TPA, SCCA, CYFRA21). The CD4/CD8 ratio and IL10 levels were significantly higher post-CCRT, while inflammation indexes (NLR, ELR) increased, and LMR decreased. The ITS, derived from 11 significant parameters, effectively predicted RE recovery, outperforming a traditional nomogram. Higher ITS scores correlated with shorter RE recovery times, as validated by Kaplan-Meier analyses and ROC curves (AUC = 0.822).

The ITS system provides a robust and reliable tool for predicting RE recovery in cervical cancer patients undergoing CCRT, surpassing traditional models in accuracy and reliability. This tool enables better patient management by allowing for timely interventions and personalized treatment strategies. Future research should focus on validating these findings in larger cohorts and integrating additional clinical parameters to enhance the predictive power of the ITS.

Cancer cell membrane-derived biomimetic nanovaccines have shown tremendous potential in cancer immunotherapy. However, their efficacy is restricted by the insufficient cross-presentation of cell membrane-associated antigens. Saposins (SAs), which are vital for membrane vesicle disintegration and cell membrane-associated antigen presentation, are severely deficient in the antigen-presenting cells (APCs) within tumors. Herein, we propose a complementary strategy for increasing the efficacy of biomimetic nanovaccines via the use of SAs. Biomimetic nanovaccines were designed using cancer cell membrane shells to provide a comprehensive array of tumor-associated antigens and reactive oxygen species (ROS)-responsive nanoparticle cores that allowed the codelivery of cytosine-guanine dinucleotides (CpGs) and SAs. The biomimetic nanovaccines were ROS-responsive and highly internalized by APCs, which enabled the release of CpGs and SAs in the endo/lysosomes of APCs. Furthermore, biomimetic nanovaccines increased the activation of immunosuppressive APCs and enhanced T-cell priming by delivering SAs to the APCs. Consequently, biomimetic nanovaccines loaded with SAs not only suppressed tumor growth but also exhibited excellent therapeutic effects in combination with immune checkpoint blockade strategies. Overall, our study provides insights into the development of enhanced biomimetic nanovaccines via integrating SAs and offers a promising strategy for highly effective cancer immunotherapy.

Endoplasmic reticulum (ER) stress is extensively studied as a pivotal role in the pathological processes associated with intestinal microecology. In antineoplastic drug treatments, ER stress is implicated in altering the permeability of the mechanical barrier, depleting the chemical barrier, causing dysbiosis, exacerbating immune responses and inflammation in the immune barrier. Enteric dysbiosis and intestinal dysfunction significantly affect the circulatory system in various heart disorders. In antineoplastic drug-related cardiovascular (CV) toxicity, ER stress constitutes a web of relationships in the host-microbiome symbiotic regulatory loop. Therefore, understanding the holobiont perspective will help de-escalate spatial and temporal restrictions. This review investigates the role of ER stress-mediated gut microecological alterations in antineoplastic treatment-induced CV toxicity.

Renal cell carcinoma (RCC) is characterised by its immunogenic and proangiogenic nature and its resistance to conventional therapies. The advent of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) has significantly improved patient survival, but resistance to these treatments remains a challenge. B7-H3, a potential immune checkpoint, has been implicated in modulating the tumour microenvironment and immune escape mechanisms in RCC.

Immunohistochemical analysis of B7-H3 expression was performed in 84 metastatic RCC patients. Tissue microarrays and separate sections of formalin-fixed paraffin-embedded tissue were used for immunohistochemical staining. Membranous staining of the tumor cells was scored and statistical analyses were performed to assess the correlation between B7-H3 expression and treatment outcome.

B7-H3 expression was absent in 31% of patients, while 33.3% had a score of 1+, 31% had 2+, and 4.8% had 3+. High B7-H3 expression correlated with poorer OS (20 months vs. 45 months, p = 0.012). In patients receiving nivolumab, those with high B7-H3 expression had shorter PFS (2 months vs. 8 months, p = 0.037) and OS (17 months vs. 51 months, p = 0.01). B7-H3 expression was the only factor significantly affecting PFS and OS in multivariate analysis.

High B7-H3 expression is associated with poorer survival outcomes and reduced response to nivolumab in metastatic RCC patients. B7-H3 may serve as a predictive biomarker for immunotherapy response. Future studies should explore targeting B7-H3 in combination with existing therapies to enhance treatment efficacy.

Type I interferons (IFNs) are essential for activating dendritic cells (DCs) and presenting tumor-associated antigens to T cells. IFNs are primarily produced from DCs among immune cells. A combination of chemotherapy and metalloimmunotherapy induces IFN production by activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. However, chemotherapeutic agents deplete DC populations, suppressing immunostimulatory activities, despite their potent anticancer activities. Furthermore, an optimal ratio between chemotherapeutic agents and metal for activating DCs at the highest level has not been reported, and evidence for ensuring DC survival is lacking. In this study, we hypothesized that there is an optimal ratio to yield the highest DC maturation and anticancer activity with minimal DC depletion. To demonstrate it, we have designed a pH and redox dual-responsive nanoparticle, MnO2@BSA@DOX (MD), to prevent DCs from depleting and activate the cGAS-STING pathway both in cancer cells and DCs, inducing considerable levels of IFNs and maturation. MD consists of a core-layer structure, a manganese dioxide (MnO2) core, and a cross-linked layer with bovine serum albumin (BSA) and doxorubicin (DOX), with a specific ratio of DOX to manganese. MD exhibits structure-based selectivity between cancer cells and DCs by targeting the extracellular pH of the tumor microenvironment and intracellular redox reactions in cancer cells. Among various formulations, the 1:1 ratio shows the highest maturation with no significant depletion. Moreover, it induces distinct cytotoxicity in cancer cells through apoptosis and cGAS-STING activation, leading to increased calreticulin expression and enhanced DC phagocytosis. Consequently, it results in superior tumor suppression and prolonged survival with the high accumulation of MD in the tumor and no observed systemic toxicities, highlighting its potential as a therapeutic agent in cancer treatments.

Colorectal cancer (CRC) remains a significant global health challenge, ranking third in incidence and second in mortality among all cancers [...].

Chemotherapy with cytotoxic drugs remains the core treatment for cancer but, due to the difficulty to find general and usable biochemical differences between cancer cells and normal cells, many of these drugs are associated with lack of specificity, resulting in side effects and collateral cytotoxicity that impair patients' adherence to therapy. Novel cancer treatments in which the cytotoxic effect is maximized while adverse effects are reduced can be implemented by developing targeted therapies that exploit the specific features of cancer cells, such as the typical expression of aberrant glycans. Modification of drug delivery systems with lectins is one of the strategies to implement targeted chemotherapies, as lectins are able to specifically recognize and bind to cancer-associated glycans expressed at the surface of cancer cells, guiding the drug treatment towards these cells and not affecting healthy ones. In this paper, recent advances on the development of lectin-modified drug delivery systems for targeted cancer treatments are thoroughly reviewed, with a focus on their properties and performance in diverse applications, as well as their main advantages and limitations. The synthesis and analytical characterization of the cited lectin-modified drug delivery systems is also briefly described. A comparison with free-drug treatments and with antibody-modified drug delivery systems is presented, emphasizing the advantages of lectin-modified drug delivery systems. Main constraints and potential challenges of lectin-modified drug delivery systems, including key difficulties for clinical translation of these systems, and the required developments in this area, are also signalled.

The combination regimen with immune checkpoint inhibitors (ICIs) and other therapies has been widely applied for patients with non-small-cell lung cancer (NSCLC). To date, no literature has systematically addressed the risk of hepatitis associated with the combination therapy. We conducted this pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS).

A total of 587,016 NSCLC reports were extracted from FAERS database spanning from the first quarter of 2013 to the second quarter of 2023. After filtering duplicate reports, logistic regression model was used to detect safety signals, and multivariable logistic regression model was used to confirm the interaction between ICI and other drugs.

Of the 81,512 patients with NSCLC, 2785 cases developed hepatitis. Multivariable logistic regression analyses revealed that the adjusted ROR of ICI combined with targeted therapy (TT) was the highest 1.64 (95% CI, 1.32-2.02; P < 0.0001) among all therapies, while that of TT and ICI treatment were 1.07 (95% CI, 0.98-1.17; P = 0.1097) and 1.12 (95% CI, 1.03-1.22; P = 0.0111), respectively. The adjusted ROR for the interaction effect was 1.64 (95% CI, 1.32-2.02; P < 0.0001). Furthermore, the adjusted ROR of ICI combined with KRAS-targeted drugs was the highest 3.03 (95% CI, 1.49-5.93; P = 0.0016) among all targeted drugs, with an adjusted ROR of 3.03 (95% CI, 1.49-5.93; P = 0.0016), indicating a meaningful interaction of these two kinds of drugs.

We confirmed that combination treatment of ICI and TT is associated with the amplified risk of hepatitis, which is partly due to the interaction between ICI and TT, and the KRAS-targeted drugs may harbor the highest potential for hepatitis induction among TT drugs when combined with ICI. Besides, the combination treatment of ICI- and KRAS-targeted drugs also increases the incidence of colitis, pulmonary embolism and dehydration.

Background: The stabilization of droplets in Pickering emulsions using solid particles has garnered significant attention through various methods. Cellulose and chitin derivatives in nature offer a sustainable source of Pickering emulsion stabilizers. Methods: In this study, medium-chain triglycerides were used as the oil phase for the preparation of emulsion. This study explores the potential of cellulose nanocrystals (CNC) and shell oligosaccharides (COS) as effective stabilizers for achieving stable Pickering emulsions. Optical microscopy, CLSM, and Cyro-SEM were employed to analyze CNC/COS-Cur, revealing the formation of bright and uniform yellow spherical emulsions. Results: CLSM and SEM results confirmed that CNC/COS formed a continuous and compact shell at the oil-water interface layer, enabling a stable 2~3 microns Pickering emulsion with CNS/COS-Cur as an oil-in-water emulsion stabilizer. Based on FTIR, XRD, and SEM analyses of CNC/COS, along with zeta potential measurements of the emulsion, we found that CNC and COS complexed via electrostatic adsorption, forming irregular rods measuring approximately 200-300 nm in length. An evaluation of the DPPH radical-scavenging ability demonstrated that the CNC/ COS-Cur Pickering emulsion performed well in vitro. In vivo experiments involving full-thickness skin excision surgery in rats revealed that CNC/COS-Cur facilitated wound repair processes. Measurements of the MDA and SOD content in healing tissues indicated that the CNC/COS-Cur Pickering emulsion increased SOD levels and reduced MDA content, effectively countering oxidative stress-induced damage. An assessment based on wound-healing rates and histopathological examination showed that CNC/COS-Cur promoted granulation tissue formation, fibroblast proliferation, angiogenesis, and an accelerated re-epithelialization process within the wound tissue, leading to enhanced collagen deposition and facilitating rapid wound-healing capabilities. An antibacterial efficacy assessment conducted in vitro demonstrated antibacterial activity.