A Kinome-Wide Synthetic Lethal CRISPR/Cas9 Screen Reveals That MTOR Inhibition Prevents Adaptive Resistance to CDK4/CDK6 Blockade in HNSCC

Overview

Journal Cancer Res Commun

Specialty Oncology

Date 2024 Jul 2

PMID 38954773

Authors

Yusuke Goto

Keiichi Koshizuka

Toshinori Ando

Hiroki Izumi

Xingyu Wu

Kuniaki Sato

Tomohiko Ishikawa

Kyle Ford

Xiaodong Feng

Zhiyong Wang

Nadia Arang

Michael M Allevato

Ayush Kishore

Prashant Mali

J Silvio Gutkind

Affiliations

Soon will be listed here.

Abstract

Significance: A kinome-wide CRISPR/Cas9 screen identified cell-cycle inhibition as a synthetic lethal target of mTORis. A combination of mTORi and palbociclib, a CDK4/6-specific inhibitor, showed strong synergistic effects in HNSCC. Mechanistically, mTORis inhibited palbociclib-induced increase in CCNE1.

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