Somatic mutations Flashcards
Somatic mutation
variations are found within the tumor
non-inheritable
Germline mutations
inheritable variations within an individual
Mutations can be used to identify
predictive markers to identify subpopulations of patients most likely to respond to therapy
Non-small lung cancer (NSCLC)
NSCLC is 85% of lung cancer cases
Tx is Platinum-based chemo, tx linked to biomarkers can overcome drug resistance
Resistance reduces survival rate
EGFR
family overexpressed in cancers, constitutively active, can indicate different cancer phenotypes
if mutation is present use TKI inhibitors, if not use chemo based tx
TKI domains is within EGFR receptor
can constitutively activate the receptor
Mutations that increase susceptibility
exons 18,19, and 21
Mutations with resistance to EGFR
TKIs are located on exon 20
cytotoxic agents
Gefitinib/Erlotinib/Afatinib
lung EGFR
PO administered
deletions in exon 19
L858R mutation in exon 21
Constitutively active
commonly found in women, asians, and never smokers
Gefitinib
no survival benefit in patients who had high levels of EGFR
Erlotinib and Afatinib
1st line tx in NSCLC pts with exon 19 deletion
exon 21 substitution
Erlotinib
interactions with 3A4 substrates
smoking decreases conc.
Afatinib drug interactions
P-gp substrate
increase exposure when co-admin with p-gp inhibitors
p-gp inducers decrease afatinib exposure
Clinical barrier
often begin tx before genotype results
Cetuximab/Panitumumab
inhibit the growth and survival of tumor cells with overexpressed EGFR
