Molecular abnormalities and cellular signaling pathways alterations in lung cancer

Abstract

Lung cancer is the main cause of death worldwide despite the progress in surgical treatment, radiotherapy, chemotherapy and targeted therapy. It is accepted that the pathogenesis of cancer involves the accumulation of multiple molecular abnormalities over time that lead to acquired cell capabilities that can be categorized into the following functional groups: self-sufficiency in growth signals due to mutations in proto-oncogenes, insensitivity to anti-growth signals as a result of mutations affecting the tumor suppressor genes, inflammatory micro-environment, evading apoptosis due to up-regulation of anti-apoptotic or down-regulation of pre-apoptotic molecules, limitless replicative potential due to telomerase activation, sustained angiogenesis, tissue invasion and metastasis. Developments in molecular biology and genetics and the modern technology of microarrays have contributed to clarify the aetiology and pathogenesis of lung cancer and a great amount of studies showed more than 20 different genetic and epigenetic alterations that have been accumulated during the pathogenesis of the disease. The above alterations that lead to the accumulation of mutations are promoted by genomic instability through inhibition of apoptosis and alternative pathways.