The challenge of drug resistance in pancreatic ductal adenocarcinoma: a current overview

Francisco Quiñonero, Cristina Mesas, Kevin Doello, et al.

Abstract


Pancreatic ductal adenocarcinoma (PDAC) has one of the highest mortality rates among all cancer types. Its delayed diagnosisprecludes curative resection, thus most of the current therapies against PDAC are based on chemo- and radiotherapy.Unfortunately, these strategies are insufficient to improve its poor prognosis. Despite the advances made in chemotherapy (e.g.nab-Paclitaxel and Gemcitabine), many patients with PDAC are unable to benefit from them due to the rapid development ofdrug resistance. Currently, more than 165 genes have been found to be implicated in drug resistance of pancreatic tumors,including different integrins, mucins, NF-κβ, RAS and CXCR4. Moreover, drug resistance in PDAC is thought to be mediated bythe modulation of miRNAs (e.g. miRNA-21, miRNA-145 and miRNA-155), which regulate genes that participate in cellproliferation, invasion and metastasis. Finally, cancer stem cells are intimately related to drug resistance in PDAC due to theirability to overexpress ABC genes -involved in drug transport-, and enzymes such as aldehyde dehydrogenases -implicated incellular drug metabolism- and poly (ADP-ribose) polymerases -involved in drug-induced DNA damage repair-. Understandingthe mechanisms involved in drug resistance will contribute to the development of efficient therapeutic strategies and to improvethe prognosis of patients with PDAC.

Cite this article as: Quiñonero F, Mesas C, Doello K, Cabeza L, Perazzoli G,Jimenez-Luna C, et al. The challenge of drug resistance in pancreatic ductaladenocarcinoma: a current overview. Cancer Biol Med. 2019; 16: 688-99. doi:10.20892/j.issn.2095-3941.2019.0252


Keywords


Pancreatic ductal adenocarcinoma; chemotherapy; drug resistance; cancer stem cells; therapeutic strategies

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