Abstract
AbstractPancreatic ductal adenocarcinoma (PDAC) is characterised by early metastasis and resistance to anti-cancer therapy, leading to an overall poor prognosis. Despite continued research efforts, no targeted therapy has yet shown meaningful efficacy in PDAC; mutations in the oncogene KRAS and the tumour suppressor TP53, which are the most common genomic alterations in PDAC, have so far shown poor clinical actionability. Autophagy, a conserved process allowing cells to recycle altered or unused organelles and cellular components, has been shown to be upregulated in PDAC and is implicated in resistance to both cytotoxic chemotherapy and targeted therapy. Autophagy is thus regarded as a potential therapeutic target in PDAC and other cancers. Although the molecular mechanisms of autophagy activation in PDAC are only beginning to emerge, several groups have reported interesting results when combining inhibitors of the extracellular-signal-regulated kinase/mitogen-activated protein kinase pathway and inhibitors of autophagy in models of PDAC and other KRAS-driven cancers. In this article, we review the existing preclinical data regarding the role of autophagy in PDAC, as well as results of relevant clinical trials with agents that modulate autophagy in this cancer.
Publisher
Springer Science and Business Media LLC
Reference126 articles.
1. Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A. & Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68, 394–424 (2018).
2. Kenner, B. J., Chari, S. T., Maitra, A., Srivastava, S., Cleeter, D. F., Go, V. L. W. et al. Early detection of pancreatic cancer—a defined future using lessons from other cancers: a white paper. Pancreas 45, 1073–1079 (2016).
3. United States National Cancer Institute. Pancreatic cancer: statistics. https://www.cancer.net/cancer-types/pancreatic-cancer/statistics (2018).
4. Waters, A. M. & Der, C. J. KRAS: the critical driver and therapeutic target for pancreatic cancer. Cold Spring Harb. Perspect. Med. 8, a031435 (2018).
5. Kabacaoglu, D., Ciecielski, K. J., Ruess, D. A. & Algul, H. Immune checkpoint inhibition for pancreatic ductal adenocarcinoma: current limitations and future options. Front Immunol. 9, 1878 (2018).
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