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Review
. 2018 May:68:77-87.
doi: 10.1016/j.jbior.2017.11.007. Epub 2017 Nov 22.

Molecular and cellular mechanisms of chemoresistance in pancreatic cancer

Affiliations
Review

Molecular and cellular mechanisms of chemoresistance in pancreatic cancer

Aleksandra Adamska et al. Adv Biol Regul. 2018 May.

Abstract

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most chemoresistant cancers, and current therapies targeting cancer-associated molecular pathways have not given satisfactory results, owing in part to rapid upregulation of alternative compensatory pathways. Most of the available treatments are palliative, focussing on improving the quality of life. At present, available options are surgery, embolization, radiation, chemotherapy, immunotherapy and use of other more targeted drugs. In this review, we describe the cellular and molecular effects of current chemotherapy drugs such as gemcitabine, FOLFIRINOX (5-fluorouracil [5-FU], oxaliplatin, irinotecan, and leucovorin) and ABRAXANE (nab-Paclitaxel), which have shown a survival benefit, although modest, for pancreatic cancer patients. Nevertheless, gemcitabine remains the standard first-line option for advanced-stage pancreatic cancer patients and, as resistance to the drug has attracted an increasing scientific interest, we deliberate on the main intracellular processes and proteins vital in acquired chemoresistance to gemcitabine. Lastly, our review examines various microenvironmental factors capable of instigating PDAC to develop resistance to chemotherapeutic drugs.

Keywords: Chemoresistance; Gemcitabine; Pancreatic cancer; Tumour microenvironment.

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