East meets West: The winning combination against BRAF V600E metastatic colorectal cancer

Abstract

Metastatic colorectal cancer (mCRC) patients with BRAF V600E mutation have a poor prognosis despite the implementation of multiple treatment strategies. The integration of traditional Chinese medicine with Western medicine in treating BRAF mutant mCRC has garnered increasing attention. Recent studies indicate that combining traditional Chinese and modern Western medical approaches not only extend survival but also reduces the risk of mortality in patients with BRAF V600E mutant mCRC. This approach is particularly effective for colorectal cancer patients who have right-sided colon involvement, liver metastasis, or a history of radiotherapy or chemotherapy. In this treatment combination, traditional Chinese medicine may offer symptomatic relief and improve quality of life, while Western medicine targets the disease more aggressively with advanced pharmacological agents. Ongoing research is crucial to further elucidate the mechanisms underlying these benefits and to optimize treatment protocols.

Key Words: Traditional Chinese medicine; Western medicine; BRAF mutation; Metastatic colorectal cancer; Medicine

Core Tip: Bian et al’s study demonstrates that integrated treatment with tolerated toxicity significantly improves survival in patients with BRAF mutant advanced colorectal cancer compared to traditional Western medicine alone, especially for certain subgroups. However, while this study provides new evidence supporting combined therapies, it also has limitations, such as unclear mechanisms of action, lack of detailed treatment protocols, and a small sample size. Summarizing these new findings and addressing the study’s issues will not only aid in the clinical application of integrated treatments for colorectal cancer but also promote the development of personalized therapies for this disease.

INTRODUCTION

Advanced colorectal cancer (CRC) with BRAF mutation poses unique therapeutic challenges due to its aggressive nature and poor prognosis[1-3]. Western therapies, including BRAF inhibitors[4] and immune checkpoint inhibitors[5], have shown promising results in CRC; However, their efficacy is often limited by drug resistance and adverse effects[6]. Traditional Chinese medicine (TCM) provides a complementary strategy through its holistic approach, aiming to improve the quality of life, mitigate side effects, and potentially enhance the effectiveness of Western treatments[7-9]. Recent studies have found that the combination of TCM and Western medicine not only significantly improve overall survival but also reduces toxicity and minimizes side effects in advanced CRC patients with BRAF-mutation compared to Western medicine treatment alone[10]. These findings provide clinical evidence supporting the integration TCM and Western medicine in treatment of CRC. By harnessing the strengths of both approaches, this combination has the potential to enhance therapeutic outcomes in CRC patients with BRAF mutation[11,12].

Discoveries of the study

Metastatic CRC (mCRC) with BRAF V600E mutations is a relatively rare but highly aggressive malignancy, often associated with poor prognoses. Traditional therapies have limited efficacy in these patients, underscoring the need for novel and effective treatment strategies[3,6]. The integration of TCM with Western medicine represent a paradigm shift in managing this patient population[13]. The study screened a total of 586 patients, with 34 ultimately meeting the inclusion criteria. The patients were divided into two groups: Cohort A received TCM and Western medicine treatment (n = 24), while cohort B received only Western medicine treatment (n = 12). The results demonstrated that the combination treatment significantly extended the median overall survival from 14.2 months to 19.9 months compared to Western medicine alone (P = 0.038). This finding is clinically significant, especially in a field where each additional month of survival can profoundly impact both quality of life and treatment decisions[14].

Identification of priority population

In the study, subgroup analyses revealed that patients with right colon involvement, liver metastasis, and those receiving first-line chemotherapy showed even more pronounced benefits from the combination treatment. This suggests that tailored treatment strategies could be particularly beneficial for the specific patient profiles[15,16]. Understanding the biological interactions between TCM and Western therapies in these contexts warrants further investigation, as it may elucidate mechanisms that can be exploited in future treatments[17].

Action mechanism of combined treatment

TCM improve survival rate of CRC patients through multiple mechanisms[18]. First, TCM often emphasizes holistic approaches, aiming to enhance the body’s natural defenses while mitigating side effects associated with conventional treatments[19]. For instance, herbal medicines may possess anti-inflammatory, antioxidant, and immunomodulatory properties that could complement the cytotoxic effects of chemotherapy. Additionally, certain TCM practices might improve patient’ overall well-being and resilience during treatment, potentially leading to better adherence and outcomes[20,21].

Clinical implications

The findings of this study hold important clinical implications. Firstly, oncologists should consider integrating TCM alongside Western medicine to treat mCRC patients with BRAF V600E mutation, since the results strongly support the survival benefits of this combination[12]. Moreover, the TCM not only extends survival but also enhances the patients’ quality of life, with the one-year survival rate reaching 95.65% in the Chinese-Western medicine cohort[11]. These findings highlight the potential of integrative treatment approaches, suggesting that future guidelines should consider incorporating TCM as a complementary strategy in conjunction with traditional therapies. Additionally, subgroup analyses have identified specific patient population that may have greater benefit based on clinical factors such as tumor location and metastatic patterns. This insight paves the way for more precise and individualized treatment[22]. Furthermore, no liver, kidney, or cardiac toxicity or allergic reactions were observed with the combined treatment of TCM and Western medicine. The common adverse reactions related to TCM were diarrhea and oral mucositis, most of them are at grade one, and could be effectively alleviated through symptomatic management. This suggests that the combined treatment is safe and effective strategy for CRC patients[23-25].

Challenges and future directions

Despite the study presents compelling evidence, there are challenges and limitations with the implementation of the combination treatment. First, the small sample size of 34 patients may limit the generalizability of the findings. Thus, larger and multicenter trials are needed to validate these results and further explore the efficacy of this combination[26,27]. Additionally, rigorous methodologies should be employed to ensure that the contributions of individual components of the integrated approach are discerned effectively[7]. Furthermore, understanding the pharmacokinetics and potential interactions between TCM and Western drugs is crucial[28,29]. It is important for healthcare providers to be aware of any contraindications or adverse effects that may arise from concurrent treatments. Establishing standardized protocols for integrating TCM into oncological practice will also be essential to ensure patient safety and maximize therapeutic efficacy.

CONCLUSION

The study highlights the potential of integrated Chinese and Western medicine in extending the survival of mCRC patients with BRAF V600E mutation. Moving forward, it is essential to explore traditional and modern approaches in tandem, fostering a multidisciplinary approach to cancer treatment[30]. These findings establish a foundation for personalized and effective therapeutic strategies, ultimately improving outcomes for these patients. The management of mCRC can be more effective and compassionate with continued research and collaboration, addressing the needs of patients holistically[31].