In: Biology
B-Raf activating mutant cancer cells are more likely to be sensitive to
A. Gefitinib
B. KRAS inhibitor
C. MEK kinase inhibitor
D. all of the above
BRAF is a human gene that encodes the protein called B-Raf, it is a proto-oncogene. Proto-oncogene is a type of gene that appears normal in its normal state, they function normally. But when this gene become mutated, its function get altered, it converted into the oncogene and get involved in tumor and cancer formation.
Mitogen-activated protein kinase (MAPK) pathway is one of the most crucial pathway which control the growth, proliferation, differentiation, migration, and apoptosis. Extracellular signal-regulated kinase (ERK) pathway is one of the most studied MAPK pathway. External factors such as growth factors and mitogens activated the ERK pathway. Epidermal growth factor receptor (EGFR) is the ligand of receptor tyrosine kinases which initiates the cascade of ERK signalling that flows through RAS GTPase, which acts as a molecular on/off switch. Mutations in B-Raf, KRAS affected this signalling pathway by making it hyperactive.
So, MEK kinase inhibitor will be affective against B-Raf mutant cancer cells which will inhibit the continuous stimulation of MAPK or MEK kinase pathway. It will be the most suitable drug for this mutant cancer cell
As it has been observed that the effect of KRAS mutation also same as B-Raf mutant cell, for this reason, KRAS inhibitor will also work against B-Raf mutant cancer cell.
Gefitinib is the inhibitor of epidermal growth factor receptor's (EGFR) tyrosine kinase domain. And EGF is the ligand which activates the MAPK pathway, so if it can inhibit the EFGR tyrosine kinase domain, then it can inhibit the signalling cascade, and in turn the cancer formation. So, this drug will also work against B-Raf mutant cancer cell.