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The war against pancreatic cancer in 2020 — advances on all fronts

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.

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Fig. 1: Mechanisms driving pancreatic cancer incidence, recurrence and therapy resistance.


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Correspondence to Vikas Dudeja.

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Jain, T., Dudeja, V. The war against pancreatic cancer in 2020 — advances on all fronts. Nat Rev Gastroenterol Hepatol 18, 99–100 (2021).

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