Targeting the Microenvironment in Pancreatic Cancer

by Wen Wee Ma, MBBS
Associate Professor, Department of Medicine

Pancreatic cancer is a highly desmoplastic disease. Microscopically, the nests of cancer cells are surrounded by thick and abundant stromal tissue that is constituted by collagen, fibroblasts, stellate cells, inflammatory infiltrate and endothelial cells. Recent studies demonstrated a symbiotic relationship between the two, and the thick stroma also impedes the penetration of cytotoxic drugs into the tumor. (Ref 1) Fibroblast growth factor receptor (FGFR) signaling has been implicated in pancreas carcinogenesis and plays a role in tumor-stromal regulation.

Targeting of the FGFR signaling is a focus of our group, and we recently reported the result of a preclinical study in the British Journal of Cancer showing that this molecular pathway is a potential therapeutic target in pancreatic cancer. (Ref 2) The result underlies the rationale for two clinical trials using dovitinib, a multikinase small molecule inhibitor with high potency against FGFRs. Other targets of dovitinib include VEGFRs and PDGFRs. The first trial (NCT01497392) combining dovitnib with gemcitabine and capecitabine is currently enrolling patients; the second trial (NCT02048943) of dovitinib with gemcitabine and nab-paclitaxel (Abraxane®) in advanced pancreatic cancer patients will be activated soon.

References

  1. Science. 2009 Jun 12;324(5933):1457-61.
  2. British Journal of Cancer. (2014) 110, 320–329.