Genome editing of LKB1 gene by CRISPR/Cas9 in lung cancer in vivo and evaluation of its role in metformin response.

Abstract

Cancer is a pathology characterized by the accumulation of mutations in the DNA of cells, these mutations may be associated with the processes of angiogenesis, inflammation, and tumor innervation. Currently, the process of tumor innervation has been described as a key process for angiogenesis and tumor inflammation. However, the tumor innervation signaling pathways are still unclear. It is known that tumor metabolism is very important, metabolic regulation may be associated with the process of tumor innervation, since ATP is a molecule classified in the literature assensors for afferent nerves sensitivity via P2X and P2Y receptors. Thereby tumor metabolism, and the ATP production can have great meaning in the process of tumor innervation. Thus, using an in vivo genetic cancer model this project aims to generated a CRISPR/Cas9-Cre dependent system in the lung of animals with mutations in KRAS and TP53 and with the presence or absence of STK11. Then, the association with pharmacological treatment with metformin, will allow to evaluate the relationship between metabolism and tumor microenvironment processes, including angiogenesis,inflammation and innervation.