Details

Autor(en) / Beteiligte

• Martins, Carla P.

Titel

Abstract IA14: Exploiting the metabolic dependencies of mutant Kras lung tumors

Ist Teil von

• Molecular cancer research, 2020-05, Vol.18 (5_Supplement), p.IA14-IA14

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Abstract Lung adenocarcinoma (LUAD) is a major cause of cancer-related death worldwide. Kras and TP53 (p53) are the most frequently mutated genes in LUAD (~30% and ~50% of LUAD cases, respectively). Since mutations in these genes cannot be currently targeted in the clinic, alternative approaches to target these aggressive and largely therapy-resistant tumors are needed. To identify new vulnerabilities associated with these tumors, our lab is characterizing the alterations that promote the development, and enable the maintenance, of mutant Kras, p53-deficient lung tumors. Using mouse models that closely recapitulate human LUAD, we have recently shown that low- and high-grade tumors exhibit distinct genetic, transcriptional, and metabolic signatures, which in turn influence their therapeutic susceptibilities. In particular, we have shown that mutant Kras gene dosage and the type of p53 mutation present have a major impact on lung tumor metabolism in vivo, creating unique dependencies that can be exploited to selectively target specific mutant Kras lung tumor subsets. This phenotypic heterogeneity is also present in the human disease and may have contributed to the poor therapeutic responses often associated with mutant Kras LUAD. We will discuss these findings and how unique metabolic signatures can be potentially exploited to improve lung cancer targeting in the clinic. Citation Format: Carla P. Martins. Exploiting the metabolic dependencies of mutant Kras lung tumors [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr IA14.