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Semin Cancer Biol. 2015 Dec;35:11-9. doi: 10.1016/j.semcancer.2015.09.011. Epub 2015 Sep 25.

Unraveling the complexity of autophagy: Potential therapeutic applications in Pancreatic Ductal Adenocarcinoma.

Author information

1
Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
2
Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands; Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, Pisa, Italy.
3
Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: gj.peters@vumc.nl.

Abstract

Autophagy is a highly dynamic, evolutionary conserved cellular homeostatic process that occurs at baseline levels in most cells. It exerts predominantly cytoprotective effects by removing damaged organelles and protein aggregates. In cancer, however, autophagy acts as both a tumor suppressor by preventing ROS-induced tumorigenesis and as a tumor inducer by providing nutrients to tumor cells under hypoxic, low-energy conditions and protecting them against therapeutically induced stress. Pancreatic Ductal Adenocarcinoma is an extremely lethal and aggressive neoplasm with a 5 year-survival rate between 1% and 5%. One of the most important factors affecting its poor prognosis is its high resistance to most of the existing chemotherapeutic regimens. The role of autophagy in PDAC has been investigated by different research groups and the results are quite divergent; some research lines point at autophagy as a tumor promoting mechanism, whereas other studies assign oncosuppressive functions to it. Nevertheless, several distinct preclinical studies and clinical trials have evaluated the efficacy of both autophagy inducers and autophagy inhibitors as therapeutic compounds against PDAC, many of them providing promising results. Although a better understanding of the complexity of autophagy is needed, the modulation of this process opens new opportunities for prognostic and therapeutic purposes.

KEYWORDS:

Autophagy; CYB5A; Chloroquine; Hydroxychloroquine; Pancreatic Ductal Adenocarcinoma; Verteporfin

PMID:
26408419
DOI:
10.1016/j.semcancer.2015.09.011
[Indexed for MEDLINE]

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