This is based on an Eastern Cooperative Oncology Group study that found that adding bevacizumab to carboplatin and paclitaxel chemotherapy for certain patients with recurrent or advanced NSCLC (stage IIIB or IV) may increase both overall survival and progression-free survival. NSCLC cells expressing programmed death-ligand 1 (PD-L1) could interact with programmed death receptor 1 (PD-1) expressed on the surface of T cells, and result in decreased tumor cell kill by the immune system. Atezolizumab is an anti PD-L1 monoclonal antibody. Nivolumab and Pembrolizumab are anti PD-1 monoclonal antibodies. Ipilimumab is a monoclonal antibody that targets Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on the surface of T cells. Bevacizumab is a monoclonal antibody that targets Vascular Endothelial Growth Factor (VEGF) in the circulation and functions as an angiogenesis inhibitor.
Other causes include radon, exposure to secondhand smoke, exposure to substances such as asbestos, chromium, nickel, beryllium, soot, or tar, family history of lung cancer, and air pollution.Genetics can also play a role as a family history of lung cancer can contribute to an increased risk of developing the disease. Furthermore, research has revealed specific chromosome regions associated with increased risks of developing lung cancer. In general, DNA damage appears to be the primary underlying cause of cancer. Though most DNA damages are repairable, leftover unrepaired DNA damages from cigarette smoke are the likely cause of NSCLC. DNA replication past an unrepaired damage can give rise to a mutation because of inaccurate translesion synthesis. In addition, during repair of DNA double-strand breaks, or repair of other DNA damages, incompletely cleared sites of repair can lead to epigenetic gene silencing. DNA repair deficiency in NSCLC
Deficiencies in DNA repair underlie many forms of cancer. If DNA repair is deficient, the frequency of unrepaired DNA damages increases, and these tend to cause inaccurate translesion synthesis leading to mutation. Furthermore, increased damages can elevate incomplete repair, leading to epigenetic alterations.As indicated as in the article Carcinogenesis, mutations in DNA repair genes occasionally occur in cancer, but deficiencies of DNA repair due to epigenetic alterations that reduce or silence DNA repair-gene expression occur much more frequently in cancer.Epigenetic gene silencing of DNA repair genes occurs frequently in NSCLC. At least nine DNA repair genes that normally function in relatively accurate DNA repair pathways are often repressed by promoter hypermethylation in NSCLC.