RAS-MAPK signaling influences the efficacy of ALK-targeting agents in lung cancer

Gorjan Hrustanovic; Trever G Bivona

doi:10.1080/23723556.2015.1091061

RAS-MAPK signaling influences the efficacy of ALK-targeting agents in lung cancer

Mol Cell Oncol. 2015 Oct 29;3(2):e1091061. doi: 10.1080/23723556.2015.1091061. eCollection 2016 Mar.

Authors

Gorjan Hrustanovic¹, Trever G Bivona¹

Affiliation

¹ Division of Hematology and Medical Oncology, University of California San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.

Abstract

ALK (anaplastic lymphoma kinase) inhibitors are approved in for ALK gene rearrangement positive (ALK+) lung cancer, but resistance remains a challenge. We discovered that RAS-RAF-MEK-ERK signaling controls the ALK inhibitor response in ALK+ lung cancer and is critical for ALK inhibitor resistance. Upfront ALK-MEK inhibitor polytherapy may enhance response and forestall resistance.

Keywords: ALK; MEK; RAS; lung cancer; resistance; targeted therapy.