Labarbarie, Bertrand (2018) Engineering of Mouse Embryonic Fibroblasts (MEFs) derived from Cas9 animals for in vitro and in vivo studies of resistance. Internship report.

Abstract

Lung cancer is the second most frequent cancer diagnosed in men (11.9%) and is the major cause of death among cancer patients (21.9%). About 80% to 85% of lung cancers are Non-small-cell lung carcinoma (NSCLC) and this specific type of cancer results in large part from the mutation of KRas, a GTPase found at the cell membrane.
The progression of premalignant cells is an evolutionary process in which mutations provide the fundamental driving force for genetic diversity. The increased mutation rate in premalignant cells allows selection for increased proliferation and survival and ultimately leads to invasion, metastasis, recurrence, and therapeutic resistance. Multiple reports have shown that the DNA cytosine deaminase enzyme Aicda (Activation Induced Cytidine Deaminase) is activated in cancer tissue (transiently or constitutively). Aicda increased level contribute to somatic mutation accumulation, cancer evolution and eventually resistance to therapy.
In this study, mouse embryonic fibroblasts (MEFs) derived from Cas9 animals have been infected with a lentiviral vector to express the oncogene KRasG12C, knock-out the tumor suppressor Trp53 and express the deaminase Aicda. The aim of the experiment was to assess if Aicda expression could influence MEFs response to a recently published KRAS inhibitor known as ARS-1620.

Item Type:	Article
Date Deposited:	01 Jan 2019 00:45
Last Modified:	01 Jan 2019 00:45
URI:	https://oak.novartis.com/id/eprint/37293