Resveratrol: A promising agent in targeting senescent cancer-associated fibroblasts to inhibit pancreatic cancer progression

Abstract

Pancreatic cancer is a highly aggressive malignancy with a poor prognosis and limited therapeutic options. The tumor microenvironment (TME), including cancer-associated fibroblasts (CAFs), plays a pivotal role in tumor progression and therapy resistance. Senescent CAFs, which exhibit a senescence-associated secretory phenotype (SASP), further exacerbate cancer growth through inflammatory cytokine secretion. This editorial highlights a study by Jiang et al, which investigates the potential of resveratrol, a natural polyphenolic compound, in targeting senescent CAFs to inhibit pancreatic cancer progression. The study demonstrates that resveratrol reduces senescent CAFs and downregulates SASP factors, thereby disrupting the pro-tumorigenic activities of these cells. Resveratrol’s ability to modulate the TME, induce apoptosis in pancreatic cancer cells, and inhibit metastasis underscores its potential as an adjunctive therapy. This research offers promising insights into novel strategies for improving therapeutic outcomes in pancreatic cancer by targeting the TME and senescent CAFs.

Keywords: Pancreatic cancer; Cancer-associated fibroblasts; Resveratrol; Tumor microenvironment; Senescence-associated secretory phenotype

Core Tip: Pancreatic cancer remains a challenging disease with limited treatment options, largely due to the tumor microenvironment (TME) and its cancer-associated fibroblasts (CAFs). Senescent CAFs, through their senescence-associated secretory phenotype (SASP), contribute to tumor progression. Recent studies have explored the potential of resveratrol, a natural polyphenolic compound, to target these senescent CAFs. Resveratrol reduces the number of senescent CAFs, downregulates SASP factors, and disrupts tumor-promoting interactions in the TME. These findings suggest that resveratrol could serve as an effective adjunctive therapy for pancreatic cancer by modulating the TME and inhibiting cancer cell proliferation and metastasis.