CXCL12 in pancreatic cancer: Its function and potential as a therapeutic drug target

Shivani Malik, Jill M. Westcott, Rolf A. Brekken, Francis J. Burrows

Research output: Contribution to journalArticlepeer-review

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a disease with limited therapeutic options and dismal long-term survival. The unique tumor environment of PDAC, consisting of desmoplastic stroma, immune suppressive cells, and activated fibroblasts, contributes to its resistance to therapy. Activated fibroblasts (cancer-associated fibroblasts and pancreatic stellate cells) secrete chemokines and growth factors that support PDAC growth, spread, chemoresistance, and immune evasion. In this review, we focus on one such chemokine, CXCL12, secreted by the cancer-associated fibroblasts and discuss its contribution to several of the classical hallmarks of PDAC and other tumors. We review the various therapeutic approaches in development to target CXCL12 signaling in PDAC. Finally, we propose an unconventional use of tipifarnib, a farnesyl transferase inhibitor, to inhibit CXCL12 production in PDAC.

Original languageEnglish (US)
Article number86
JournalCancers
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2022

Keywords

  • CXCL12
  • CXCR4
  • Cancer-associated fibroblast
  • Pancreatic cancer
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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