Clinical diagnosis and management of pancreatic cancer: Markers, molecular mechanisms, and treatment options

Table 1 Diagnostic markers of pancreatic cancer

Cancer type	Markers	Expression	Sensitivity	Specificity	AUC	Ref.
PC	CA 19-9	Serum	72.0%	86%.0	0.8474	[72]
PC	MUC5AC + CA19-9	Serum	73.8%	88.6%	0.8940	[75]
PC	MIC-1	Serum	80.0%	85.0%	0.8945	[76]
PDAC	Keratin 8	Serum	80.0%	85.0%	0.8945	[77]
PDAC	PIVKA-II	Serum	78.7%	90.7%	0.9000	[78]
PDAC	GREM1	Serum	Unknown	Unknown	0.7180	[79]

AUC: Area under the curve; CA19-9: Carbohydrate antigen 19-9; GREM1: Gremlin 1; MIC-1: Macrophage inhibitory cytokine-1; MUC5AC: Mucin 5AC; PC: Pancreatic cancer; PDAC: Pancreatic ductal adenocarcinoma; PIVKA-II: Protein induced by vitamin k absence II.

Table 2 Food and Drug Administration-approved treatments for pancreatic cancer patients

Drug names	Conditions	Targets	Ref.
Belzutifan	Pancreatic neuroendocrine tumors	An inhibitor of hypoxia-inducible factor-2α	[93,94]
Erlotinib hydrochloride	Gemcitabine hydrochloride-treated PC, not removable with surgery, with metastasis or local progression	An EGFR inhibitor	[95,96]
Everolimus	Progressive pancreatic neuroendocrine tumors, not removable with surgery, with metastasis or local advance	A mammalian target of rapamycin inhibitor	[97,98]
Fluorouracil, also called 5-FU	Pancreatic cancer	An anti-metabolite drug with multiple functions such as inhibition of cellular thymidylate synthase to prevent DNA replication and inhibit RNA synthesis	[99,100]
Gemcitabine hydrochloride	PC with metastasis, local advance, or fluorouracil treatment	An antimetabolite drug and an inhibitor of DNA synthesis	[101,102]
Irinotecan hydrochloride liposome	Metastatic PC or gemcitabine hydrochloride-treated PC with precision	An inhibitor of topoisomerase I	[103,104]
Mitomycin	Pancreatic adenocarcinoma with local advance or metastasis to other parts of the body, which has no approvement with other types of treatment	An inhibitor of DNA synthesis and thioredoxin reductase	[105,106]
Olaparib	Metastatic PC after first-line therapy with platinum chemotherapy and with certain germline mutations in the breast cancer 1 or BRCA2 gene	A poly ADP-ribose polymerase inhibitor	[107,108]
Paclitaxel albumin-stabilized nanoparticle formulation	PC with metastasis	It prevents cell mitosis and inhibits the growth of cancer cells	[109,110]
Sunitinib malate	Progressive neuroendocrine tumors that are not removable with surgery, with metastasis to other parts of the body or local advance	An antiangiogenic tyrosine kinase inhibitor	[111,112]

EGFR: Epidermal growth factor receptor; PC: Pancreatic cancer.

Table 3 Completed clinical trials with results for pancreatic cancer treatment

Trial number	Phase	Treatment	Condition
NCT01373164	1b/2	Galunisertib, a TGF-β receptor inhibitor, or placebo plus gemcitabine	Unresectable PC
NCT01423604	2	Ruxolitinib, a Janus kinase 1/2 inhibitor or placebo plus capecitabine	PC
NCT00965718	2	Activated T lymphocyte (ex vivo-expanded, CIK cells cultured with anti-CD3 monoclonal antibody and IL-2)	PC
NCT01204372	2	Gemcitabine, trastuzumab plus erlotinib	Metastatic PC
CONKO-005	3	Erlotinib (inhibits the intracellular phosphorylation of tyrosine kinase associated with the EGFR) or placebo plus gemcitabine	Primarily resectable PDAC after R0 resection
NCT02923921	3	Pegilodecakin (a pegylated recombinant human IL-10) plus folinic acid, fluorouracil, and oxaliplatin	Metastatic PDAC
NCT01494506	3	Liposomal irinotecan (it prevents the religation of the DNA strand by binding to the topoisomerase I-DNA complex.) or placebo plus 5-FU/LV	Metastatic PC
NCT01214720	3	Bevacizumab that acts by selectively binding circulating VEGF, thereby inhibiting the binding of VEGF to its cell surface receptors plus chemotherapy	Metastatic PC
NCT00428597	3	Sunitinib, an inhibitor of multiple receptor tyrosine kinases	Metastatic pancreatic neuroendocrine tumors
NCT01525550	4

5-FU/LV: 5-Fluorouracil/leucovorin; CIK: Cytokine-induced killer; EGFR: Epidermal growth factor receptor; IL: Interleukin; PC: Pancreatic cancer; PDAC: Pancreatic ductal adenocarcinoma; TGF-β: Transforming growth factor beta; VEGF: Vascular endothelial growth factor.

Table 4 Ongoing or recruiting clinical trials for pancreatic cancer treatment

Trial number	Phase	Treatments	Conditions
NCT03192462	1 or 2	Intravenous infusions of TAA-specific cytotoxic T lymphocytes	Pancreas cancer with metastatic, locally advanced unresectable, or resectable disease
NCT04637698	1 or 2	Oncolytic viral therapy (Type 2 Herpes simplex virus) expressing GM-CSF	Pancreatic cancer
NCT04247165	1 or 2	Dual checkpoint inhibition (nivolumab and ipilimumab) in combination with gemcitabine and nab-paclitaxel followed by immune-chemoradiation	Borderline resectable, locally advanced, or metastatic pancreatic cancer
NCT05141149	1 or 2	Anti-PAUF monoclonal antibody PBP1510 or in combination with gemcitabine	Advanced/metastatic pancreatic cancer
NCT04825288	1 or 2	Anti-IL-1α true human antibody XB2001 or in combination with ONIVYDE + leucovorin + 5-FU chemotherapy	Advanced pancreatic cancer
NCT03662412	1 or 2	Sirolimus, a selective inhibitor of mTOR	Advanced pancreatic cancer
NCT05131776	2 or 3	Concurrent EUS-guided intratumor injection of P-32 microparticles (OncoSil)	Locally advanced pancreatic carcinoma
NCT03941093	3	Neoadjuvant treatment with pamrevlumab or placebo in combination with either gemcitabine plus nab-paclitaxel or FOLFIRINOX	Locally advanced pancreatic cancer
NCT05529940	3	FOLFIRINOX	Resectable pancreatic cancer
NCT04969731	3	Adjuvant Immuncell-LC (Cytokine-induced killer cells) therapy combined with gemcitabine	Resectable pancreatic cancer
NCT04025840	4	Perioperative epidural block and/or dexamethasone	Resectable pancreatic cancer
NCT04217096	4	Paclitaxel liposome plus S-1, an oral anticancer drug that consists of tegafur, gimeracil, and potassium oteracil in a molar ratio of 1.0:0.4:1.0	Advanced metastatic pancreatic cancer as the first-line therapy

5-FU: 5-Fluorouracil; EUS; Endoscopic ultrasound; FOLFIRINOX: Folinic acid + fluorouracil + irinotecan + oxaliplatin; IL: Interleukin; GM-CSF: Granulocyte macrophage colony-stimulating factor; mTOR: Mammalian target of rapamycin; PAUF: Pancreatic adenocarcinoma up-regulated factor; TAA: Tumor-associated antigen.