Fer governs mTORC1 regulating pathways and sustains viability of pancreatic ductal adenocarcinoma cells

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer characterized by a poor prognosis and limited treatment options. In a study published in Frontiers in Oncology, Prof. Uri Nir, Prof. Ron Unger, and colleagues focus on the intracellular tyrosine kinase Fer, which is elevated in PDAC cells and associated with worse outcomes. Using the Fer-specific inhibitor E260 or gene knockout, the study reveals Fer's dual effect on the mTORC1 pathway, a major growth and survival mechanism for cancer cells. First, Fer inhibition induces mitochondrial deformation, leading to a shortage of key nutrients and activation of a stress response that represses mTORC1. Additionally, E260 inhibits ERK1/2, which normally prevents mTORC1 suppression by TSC2, thereby further reinforcing mTORC1 inhibition. As a result, E260 treatment of PDAC cells promotes necrotic cell death. These findings suggest that Fer is a key regulator of PDAC survival and may present a promising target for treatment.

Last Updated Date : 26/06/2025