Pancreatic Ductal Adenocarcinoma: Current and Evolving Therapies

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2017 Jun 23

PMID 28640192

Citations 302

Authors

Aleksandra Adamska

Alice Domenichini

Marco Falasca

Affiliations

Soon will be listed here.

Abstract

Pancreatic ductal adenocarcinoma (PDAC), which constitutes 90% of pancreatic cancers, is the fourth leading cause of cancer-related deaths in the world. Due to the broad heterogeneity of genetic mutations and dense stromal environment, PDAC belongs to one of the most chemoresistant cancers. Most of the available treatments are palliative, with the objective of relieving disease-related symptoms and prolonging survival. Currently, available therapeutic options are surgery, radiation, chemotherapy, immunotherapy, and use of targeted drugs. However, thus far, therapies targeting cancer-associated molecular pathways have not given satisfactory results; this is due in part to the rapid upregulation of compensatory alternative pathways as well as dense desmoplastic reaction. In this review, we summarize currently available therapies and clinical trials, directed towards a plethora of pathways and components dysregulated during PDAC carcinogenesis. Emerging trends towards targeted therapies as the most promising approach will also be discussed.

Citing Articles

tRF-Pro-CGG Suppresses Cell Proliferation and Promotes Apoptosis in Pancreatic Cancer.

Zhu J, Zhang X, Luo T, Xue C, Chao J, Li J Dig Dis Sci. 2025; .

PMID: 40056302 DOI: 10.1007/s10620-025-08943-x.

Impact of Routine and Selective Preoperative Endoscopic Retrograde Cholangiopancreatography with Stent Placement on Postoperative and Oncologic Outcomes Following Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma.

Aeschbacher P, Wenning A, Katou S, Morgul H, Juratli M, Becker F Biomedicines. 2025; 13(2).

PMID: 40002746 PMC: 11853506. DOI: 10.3390/biomedicines13020333.

Advancing Immunotherapy in Pancreatic Cancer: A Brief Review of Emerging Adoptive Cell Therapies.

Sherpally D, Manne A Cancers (Basel). 2025; 17(4).

PMID: 40002184 PMC: 11853216. DOI: 10.3390/cancers17040589.

Novel Pt (II) Complexes With Anticancer Activity Against Pancreatic Ductal Adenocarcinoma Cells.

Stefano E, Rovito G, Cossa L, Castro F, Vergaro V, Ali A Bioinorg Chem Appl. 2025; 2024:5588491.

PMID: 39886428 PMC: 11779987. DOI: 10.1155/bca/5588491.

Unveiling Microbiota Profiles in Saliva and Pancreatic Tissues of Patients with Pancreatic Cancer.

Uguz A, Muftuoglu C, Mert U, Gumus T, Ece D, Asadi M Microorganisms. 2025; 13(1.

PMID: 39858887 PMC: 11767796. DOI: 10.3390/microorganisms13010119.

References

Javle M, Shroff R, Xiong H, Varadhachary G, Fogelman D, Reddy S . Inhibition of the mammalian target of rapamycin (mTOR) in advanced pancreatic cancer: results of two phase II studies. BMC Cancer. 2010; 10:368. PMC: 2910694. DOI: 10.1186/1471-2407-10-368. View

Liu P, Liang H, Xia Q, Li P, Kong H, Lei P . Resveratrol induces apoptosis of pancreatic cancers cells by inhibiting miR-21 regulation of BCL-2 expression. Clin Transl Oncol. 2013; 15(9):741-6. DOI: 10.1007/s12094-012-0999-4. View

Kulke M, Blaszkowsky L, Ryan D, Clark J, Meyerhardt J, Zhu A . Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J Clin Oncol. 2007; 25(30):4787-92. DOI: 10.1200/JCO.2007.11.8521. View

Antoniou G, Kountourakis P, Papadimitriou K, Vassiliou V, Papamichael D . Adjuvant therapy for resectable pancreatic adenocarcinoma: review of the current treatment approaches and future directions. Cancer Treat Rev. 2013; 40(1):78-85. DOI: 10.1016/j.ctrv.2013.05.008. View

Varadhachary G, Tamm E, Abbruzzese J, Xiong H, Crane C, Wang H . Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol. 2006; 13(8):1035-46. DOI: 10.1245/ASO.2006.08.011. View

Li Y, Sarkar F . MicroRNA Targeted Therapeutic Approach for Pancreatic Cancer. Int J Biol Sci. 2016; 12(3):326-37. PMC: 4753161. DOI: 10.7150/ijbs.15017. View

Schultz N, Werner J, Willenbrock H, Roslind A, Giese N, Horn T . MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma. Mod Pathol. 2012; 25(12):1609-22. DOI: 10.1038/modpathol.2012.122. View

Xia J, Cheng L, Mei C, Ma J, Shi Y, Zeng F . Genistein inhibits cell growth and invasion through regulation of miR-27a in pancreatic cancer cells. Curr Pharm Des. 2014; 20(33):5348-53. DOI: 10.2174/1381612820666140128215756. View

Hishinuma S, Ogata Y, Tomikawa M, Ozawa I, Hirabayashi K, Igarashi S . Patterns of recurrence after curative resection of pancreatic cancer, based on autopsy findings. J Gastrointest Surg. 2006; 10(4):511-8. DOI: 10.1016/j.gassur.2005.09.016. View

10.

Le D, Lutz E, Uram J, Sugar E, Onners B, Solt S . Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. J Immunother. 2013; 36(7):382-9. PMC: 3779664. DOI: 10.1097/CJI.0b013e31829fb7a2. View

11.

Fine R, Fogelman D, Schreibman S, Desai M, Sherman W, Strauss J . The gemcitabine, docetaxel, and capecitabine (GTX) regimen for metastatic pancreatic cancer: a retrospective analysis. Cancer Chemother Pharmacol. 2007; 61(1):167-75. DOI: 10.1007/s00280-007-0473-0. View

12.

Bergers G, Song S, Meyer-Morse N, Bergsland E, Hanahan D . Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest. 2003; 111(9):1287-95. PMC: 154450. DOI: 10.1172/JCI17929. View

13.

Greer S, Pipas J, Sutton J, Zaki B, Tsapakos M, Colacchio T . Effect of neoadjuvant therapy on local recurrence after resection of pancreatic adenocarcinoma. J Am Coll Surg. 2008; 206(3):451-7. DOI: 10.1016/j.jamcollsurg.2007.10.002. View

14.

VanHouten J, White R, Jackson G . A decision model of therapy for potentially resectable pancreatic cancer. J Surg Res. 2011; 174(2):222-30. PMC: 3320682. DOI: 10.1016/j.jss.2011.08.022. View

15.

Liu C, Cheng H, Shi S, Cui X, Yang J, Chen L . MicroRNA-34b inhibits pancreatic cancer metastasis through repressing Smad3. Curr Mol Med. 2013; 13(4):467-78. DOI: 10.2174/1566524011313040001. View

16.

Munoz Martin A, Garcia Alfonso P, Ruperez A, Martin Jimenez M . Nab-paclitaxel plus gemcitabine as first-line palliative chemotherapy in a patient with metastatic pancreatic cancer with Eastern Cooperative Oncology Group performance status of 2. Oncol Lett. 2016; 12(1):727-730. PMC: 4907314. DOI: 10.3892/ol.2016.4667. View

17.

Safran H, Miner T, Bahary N, Whiting S, Lopez C, Sun W . Lapatinib and gemcitabine for metastatic pancreatic cancer. A phase II study. Am J Clin Oncol. 2014; 34(1):50-2. DOI: 10.1097/coc.0b013e3181d26b01. View

18.

Oettle H, Neuhaus P, Hochhaus A, Hartmann J, Gellert K, Ridwelski K . Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013; 310(14):1473-81. DOI: 10.1001/jama.2013.279201. View

19.

Hosein P, Macintyre J, Kawamura C, Maldonado J, Ernani V, Loaiza-Bonilla A . A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer. 2012; 12:199. PMC: 3404979. DOI: 10.1186/1471-2407-12-199. View

20.

ONeil B, Scott A, Ma W, Cohen S, Aisner D, Menter A . A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer. Ann Oncol. 2015; 26(9):1923-1929. PMC: 4551155. DOI: 10.1093/annonc/mdv264. View