Flashcards in Directed Anti-Cancer Drugs Deck (20):
What are four classes/concepts in directed anti-tumor therapies?
-attack aspects specific to tumor cells
-mark tumors specifically for attack by the immune system
-deliver chemotherapies or radiation specifically to the tumor cell
interfere with critical molecular signaling pathways
What are tyrosine kinases and why are they important in cancer?
family of signaling enzymes that catalyze tyrosine phosphorylation and often affect gene transcription downstream. Often constitutively turned "on" in cancer cells
What is the classic example of a tyrosine kinase inhibitor anti-cancer drug?
Imatinib (gleevec) (first), trastuzumab (herceptin)
How does imatinib work?
tyrosine kinase inhbitor that occupies the nucleotide binding cleft of the BCR-ABL fusion protein from the Philadelphia chromosome. Seen in chronic myelogenous leukemia and acute lymphoblastic leukemia.
What is trastuzumab?
a drug that blocks HER2 in some breast cancers. HER2 block the extracellular ligand binding site to make an effective receptor tyrosine kinase inhibitor
When are retinoids useful (type of cancer and translocation that causes it) and what is the name of the drug? How do they work?
help regulate transcription
ATRA (all trans retinoic acid) in ACUTE PROMYELOCYTIC LEUKEMIA: cause differentiation from immature cell to mature cell.
(also accutane in neuroblastoma)
Define whole cell vaccines for tumors.
target APCs inside the body so that they take up and present the tumor antigens to T cells.
Define antigen therapy vaccines.
target APCs so that they present tumor antigens to T cells.
Define antigen-presenting cell vaccines.
injection of modifed antigen presenting cells from the lab into the patient to stimulate T cells.
What are the three theoretical types of cancer vaccines?
whole cell, antigen therapy, antigen presenting cells
What is the target of most anti-angiogenesis cancer therapies?
What do monoclonal antibodies do?
change signal transduction and block ligand receptor interaction. Also stimulate the immune response. May be tied to a cytotoxic agent.
Problems are with large size that may limit tumor penetration and distribution.
What monoclonal antibodies should I know? For what disease?
Rituximabe with is against CD20 (cell cycle regulation)
treats non-hodgkin lymphoma
Also bevacizumab/avastin, that targets VEGF
What is bevacizumab?
monoclonal antibody that targets VEGF
What is the Skipper-Schabel-Wilcox model of tumor growth?
predicts logarithmic tumor growth where doubling time is constant
this suggests that growth rate, tumor bulk, and chemotherapy bulk determines outcome.
doesn't account for the fact that doubling time is not fixed, you can't deliver high enough doses, and doesn't account for resistance
What is gompertzian growth model?
suggests that tumor growth is a sigmoid curve- fastest when the tumor is smaller, often when it is subclinical.
What is the Norton-Simon model?
Models response of tumors to chemotherapy assuming the gompertzian model. suggests we should use multiple sequential agents at high doses and alternating regimens
What model explains the model of genetic resistance to cancer?
Goldie-Coldman model. suggests that even small tumors have multiple resistant clones.
What is the Goldie-Coldman model?
model that explains resistance of tumors to chemotherapy: genetic instability is such that some clones will be resistant even at baseline.
treat in alternating regimens