The most frequent cancer related deaths have been associated with lung
cancer. The subtypes, Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung
Cancers (SCLC), respond to chemical drugs and radiotherapy. NSCLC (60%) express
membrane epidermal growth factor receptor (EGFR). The cell signalling pathway
induced by EGFR has been attributed as a key reason for lung cancer progression.
There are many FDA approved drugs available for the treatment which primarily
includes EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib, or
EGFR neutralizing antibody, necitumumab. However, the reports suggest that EGFR
can undergo further mutation in tyrosine kinase domain which makes the cells resistant
to the ongoing treatment. Alternate signalling pathways may get activated accompanied
by epithelial mesenchymal transition and imbalanced microRNAs that contribute
towards resistance. Epigenetic changes in lung cancer also offer dynamic targets for
cancer therapy. The agents targeting epigenetic changes can be combined with
chemotherapy or other-directed therapy so that effective dose and hence toxicity is
reduced with enhanced efficacy. Micro-RNAs are the largest class of the gene
regulators that regulate the cancer genes. Inhibiting or replacing the cancer-causing
miRNAs can be potential targets for cancer treatment. Researchers have also worked
on immunotherapy drugs like nivolumab, pembrolizumab and atezolizumab, which
reverse the inhibitory mechanism of the immune response. New findings from recent
trails provide an optimistic perspective on the progress towards the better treatment of
lung cancer.
Keywords: EGFR, Epigenetic, Immunotherapy, miRNA, PD-1/PDL-1, T790M
mutation.
