In 2020, important advances were made across three major frontiers of pancreatic ductal adenocarcinoma (PDAC) research: risk factors, therapeutic resistance and tumour recurrence. Pathophysiology of obesity-mediated PDAC initiation was elucidated, novel stromal mechanisms of therapeutic resistance were unveiled and the genetic evolution of recurrent PDAC under therapeutic pressures was tracked in human samples.
Key advances
-
An endocrine–exocrine axis involving cholecystokinin secretion by remodelled β-cells drives obesity-mediated pancreatic ductal adenocarcinoma (PDAC) progression, and this process can be intercepted through weight loss strategies4.
-
Novel avenues for stromal manipulation to improve PDAC therapy were identified in the form of LCCR15+ cancer-associated fibroblasts, which can be used to predict immunotherapy resistance7.
-
Whole-exosome sequencing of primary tumour and matched autopsy samples from patients with recurrent PDAC demonstrated treatment-induced genetic bottlenecks and intermetastatic seeding leading to subclonal heterogeneity in the recurrent tumours, also identifying potentially targetable genetic signatures in recurrent disease9.
This is a preview of subscription content, log in via an institution to check access.
References
Bray, F. et al. 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).
Strobel, O. et al. Optimizing the outcomes of pancreatic cancer surgery. Nat. Rev. Clin. Oncol. 16, 11–26 (2019).
Zhou, B. et al. Obesity and pancreatic cancer: an update of epidemiological evidence and molecular mechanisms. Pancreatology 19, 941–950 (2019).
Chung, K. M. et al. Endocrine-exocrine signaling drives obesity-associated pancreatic ductal adenocarcinoma. Cell 181, 832–847 (2020).
Garg, B. et al. NFκB in pancreatic stellate cells reduces infiltration of tumors by cytotoxic T cells and killing of cancer cells, via up-regulation of CXCL12. Gastroenterology 155, 880–891 (2018).
Kleeff, J. et al. Pancreatic cancer. Nat. Rev. Dis. Primers 2, 16022 (2016).
Dominguez, C. X. et al. Single-cell RNA sequencing reveals stromal evolution into LRRC15 + myofibroblasts as a determinant of patient response to cancer immunotherapy. Cancer Discov. 10, 232–253 (2020).
Öhlund, D. et al. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J. Exp. Med. 214, 579–596 (2017).
Sakamoto, H. et al. The evolutionary origins of recurrent pancreatic cancer. Cancer Discov. 10, 792–805 (2020).
Makohon-Moore, A. P. et al. Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer. Nat. Gen. 49, 358–366 (2017).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Rights and permissions
About this article
Cite this article
Jain, T., Dudeja, V. The war against pancreatic cancer in 2020 — advances on all fronts. Nat Rev Gastroenterol Hepatol 18, 99–100 (2021). https://doi.org/10.1038/s41575-020-00410-4
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41575-020-00410-4
- Springer Nature Limited
This article is cited by
-
Intelligent nanovesicle for remodeling tumor microenvironment and circulating tumor chemoimmunotherapy amplification
Journal of Nanobiotechnology (2024)
-
Pirfenidone alleviates fibrosis by acting on tumour–stroma interplay in pancreatic cancer
British Journal of Cancer (2024)
-
A novel immune checkpoint score system for prognostic evaluation in pancreatic adenocarcinoma
BMC Gastroenterology (2023)
-
A self-amplifying USP14-TAZ loop drives the progression and liver metastasis of pancreatic ductal adenocarcinoma
Cell Death & Differentiation (2023)
-
Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review
Signal Transduction and Targeted Therapy (2023)