Cancer Genetics Flashcards
gleevec (imatinib)
inhibits the constitutively active kinase that arises from the philadelphia chromosome (bcr-abl) for treatment of CML
oncogene addiction
cancer cells depend on one or a few oncogenes for cell survival, which is a rationale for targeted therapy
chemotherapy
acts on DNA to kill proliferating cells (cytotoxic); can not differentiate between normal and cancer cells
chemo drugs
alkylating agents and platinum based drugs, topoisomerase inhibitors, taxanes (disrupt MT)
targeted therapy
inhibit a specific target in cancer cells - mutant proteins, fusion proteins, etc.
targeted therapy drugs
small molecular inhibitors (TKIs and proteasome inhibitors) and antibodies
“nib”
tyrosine kinase inhibitors; inhibit ATP from binding for function
“mib”
proteasome inhibitors
“mab”
monoclonal antibodies; prevent receptor activation
driver mutations
primary force for promoting cancer formation and are a potential target for therapy
causes of driver mutations
over expression, amplification, mutations
examples of driver mutations
BCR/ABL, ALK, EGFR, HER-2, Ras, Myc
HER family
epidermal growth factor receptors; frequently mutated in lung and breast cancer due to activation in absence of ligand
EGFR’s act via _
tyrosine kinase that phosphorylates factors needed for cell proliferation, survival, invasion, metastasis, and chemo resistance
EGFR-mutated cells depend on _
a functional EGFR for their survival, rendering them addicted to the receptor
EGFR main pathways
Akt and K-ras–>Mek/Erk
HER1 mutation associated with _
non-small cell lung cancer (NSCLC)
HER1 mutation hot spots
exon 19-21, corresponding with tyr kinase domain
targeting EGFR
EGFR-TK inhibitors and anti-EGFR monoclonal antibodies
anti-EGFR mAb’s
prevent ligand from binding and will also cause receptor internalization that leads to degradation
mutation resistant to TKIs
T790M in exon 20 of HER1
primary resistance
mutation exists in tumor at time of treatment
secondary resistance
acquired mutation after treatment
common reasons for resistance to TKIs
amplification of Met oncogene allows bypassing of EGFR and PI3K mutations often co-occur with EGFR mutations
