Abstract B22: Acyl-CoA synthetase long-chain family member 3 dependent lipid homeostasis is required for mutant KRAS driven lung cancer

Lung cancer is the leading cause of cancer related deaths in the USA and worldwide. Lung tumorigenesis is a multistep process that involves several genetic aberrations. Activating mutations of the proto-oncogene KRAS (mutant KRAS) occur in ~30% of the cases of human non-small cell lung cancer (NSCLC), which is associated with aggressive, therapy-resistant disease. Despite the recent discovery of low affinity inhibitors, mutant KRAS is a challenging therapeutic target and there is a dearth of therapeutic options for these tumors. Mutant KRAS not only promotes tumorigenesis but also the survival of established lung cancer, both in mouse models and in certain human NSCLC lines. Therefore, in the absence of clinically-relevant effective inhibitors of mutant KRAS, there has been an intense clinical interest in the development of inhibitors of its downstream effectors. Importantly, mutant KRAS cancer cells undergo oncogene-directed metabolic reprogramming in order to meet the energetic and biosynthetic challenges of cell survival, growth and proliferation. Activation of certain pathways of fatty acid synthesis has been observed in many cancer types including lung cancer. Till date, fatty acid synthase (FASN) has been the candidate for drug development. Unfortunately, the inhibitors against FASN have poor pharmacokinetics and target related toxicity concerns. There is an urgent need for discovery of additional targets that inhibit lipid metabolism specifically in cancer cells that c...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Signaling Pathways and Cancer Metabolism: Poster Presentations - Proffered Abstracts Source Type: research