Rx for Lung Cancer- Sweatman Flashcards
Name 3 mechanisms of resistance to TKIs
1) Drug binding site mutation (highly conserved ATP binding site)
2) Compensatory Tyrosine phosphorylation by MET
3) MET assumes an independent role in the proliferative signaling process
What are the 2 common downstream mutations in the EGFR/Tyrosine Kinase complex pathway?
Constitutive activation of KRAS or BRAF
What effect does downstream mutation have on drug therapy?
It renders it useless
What is the effect of the EML4-ALK oncogene?
Activation of MEK/ERK, subsequent proliferation
Who is the EML4-ALK mutation seen in?
Non-smokers and those with adenocarcinomas
What is the mechanism for VEGF release?
Hypoxia is sensed by the cell–> induces HIF-1–>HIF-1 translates to the nucleus–>VEGF is transcribed–>Angiogenesis
What TKI is used against EML4-ALK?
Crizotinib
What TKI is used against EGFR?
Erlotinib
What is the gold standard CONVENTIONAL chemo treatment for SCLC?
Etoposide + cisplatin or carboplatin
When is Erlotinib first line therapy?
Treatment of locally advanced or metastatic NSCLC after failure of at least one prior chemo regimen
Mechanism of 6-Mercaptopurine, 6-Thioguanine, and Methotrexate therapy?
Inhibits purine ring synthesis; the first 2 interrupt elongation after incorporation into the strand; MTX is a DHFR antagonist
Mechanism of Hydroxyurea?
Inhibits ribonucleotide reductase
Mechanism of 5-Fluorouracil?
Inhibits dTMP synthesis
Mechanism of Cytarabine?
Inhibits DNA synthesis (antimetabolite)
Mechanism of Bleomycin?
Acts as molecular scissors to cut DNA strands
Mechanism of the Anthracyclines?
Intercalate DNA; also produces free radicals (where the cardiomyopathy comes from)
Mechanism of the alkylating agents, Nitrosureas, and Platinum drugs?
Cross-link DNA
Mechanism of L-aspariginase?
Inhibits protein synthesis
Mechanism of Taxanes and Vincas?
Inhibit microtubule function; Taxanes stabilize and Vincas prevent formation
Unique toxicities of the platinum drugs?
Ototoxicity and Nephrotoxicity
Unique toxicity of cyclophosphamide and ifosfamide? What is given with it to prevent this?
Hemorrhagic cystitis (more so cyclophosphamide); mesna protects the bladder
Unique toxicities seen in the taxanes and vincas? What clinical finding helps you diagnose this?
Peripheral neuropathy; loss of deep tendon reflex
Unique toxicity of the anthracylcines (doxorubicin, daunorubicin, and idrarubicin)? What is given to protect against it?
Cardiomyopathy–>CHF; co-administer with dexrazoxane
What are some downsides to oral therapy (TKIs)?
Interactions with CYP, P-gp efflux pumps, first-pass metabolism, and drug drug interactions
