Glutaminase as a metabolic target of choice to counter acquired resistance to Palbociclib by colorectal cancer cells.

ABSTRACT: Several mechanisms of resistance of cancer cells to cyclin-dependent kinase inhibitors (CDKi) have been identified, including the upregulation of metabolic regulators such as glutaminase. However, whether such resistance mechanisms represent optimal targets has not been determined. Here, we have systematically analyzed metabolic reprogramming in colorectal cancer cells exposed to Palbociclib, a CDKi selectively targeting CDK4/6, or Telaglenastat, a selective glutaminase inhibitor. Through multiple approaches, we show that Palbociclib and Telaglenastat elicit complementary metabolic responses and are thus uniquely suited to counter the metabolic reprogramming induced by the reciprocal drug. As such, while Palbociclib induced reduced tumor growth in vivo, and Telaglenastat did not show a sig

SUBMITTER: Tarrado-Castellarnau M 

PROVIDER: S-EPMC12399431 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature