Researchers from the Johns Hopkins Kimmel Cancer Center have discovered a novel cell signaling pathway that could be targeted in therapy for patients with aggressive pancreatic cancers. The High Mobility Group A1 (HMGA1) protein functioned as a “molecular switch” that “flipped on” genes required by tumor cells to grow in an uncontrollable manner and form invasive tumors. One of these genes activated by HMGA1 leads to the production of fibroblast growth factor 19 (FGF19), which coaxes tumor cells to grow quickly and invade surrounding tissues. Both HMGA1 and FGF19 cooperate to “build” a dense, fibrous, scar-like wall around the tumor cells, which is known as the stroma. When scientists disrupted FGF19 signals in mouse models of pancreatic cancer, tumor cells had markedly decreased growth and less stroma formation, suggesting that drugs to block FGF19 signals already available for use by patients with other diseases could be repurposed to treat pancreatic tumors that have high levels of FGF19. The study was published online in The Journal of Clinical Investigation. This paradigm is a promising target for the development of new treatments for pancreatic cancer.
