Question

T790M mutation in epidermal growth factor receptor (EGFR) causes resistance to several EGFR tyrosine kinase inhibitors that are used for treatment of non-small cell lung cancer (NSCLC). To reduce resistance, new drug or other chemical interventions are needed. Please design a “Co-Clinical Trial” to target this mutation.

Answer 1

T790M is basically a gatekeeper mutation that occurs in EGFR and during this mutation the threonine is substituted with a methionine in the 20^th exon at position 790. This leads to affect the ATP binding pocket. Due to the mutation, it tends to resist many EGFR tyrosine kinase inhibitors and hence it causes a hindrance to the treatment to the non-small cell lung cancer. The vector introduction also leads to causing of gefitinib resistance and hence it was found that T790M causes tumors which are sensitive and become resistance to the EGFR tyrosine kinase inhibitors.

The co-clinical trial can be conducted using people and causing a mutation in the T790M to see if there is an uplift in the resistance mechanism and if it still acts as prognostic factor for the non-small cell lung cancer. The mutation can be trigger to alter the gene expression to lift the resistance to check if that can treat the cancer.