Cancer Therapy - Dr. Kamath

Front 1

pro-apoptic proteins

Back 1

Bad, Bax, Bak

Front 2

pro-survival (Anti-apopoptic protein)

Back 2

Bcl-2, Bcl-X

Front 3

What are the 3 types of cytotoxic therapies? what are their targets and which phase of the cell cycle do they affect?

Back 3

1. antimetabolites - 5fu, methotextrate - DNA synthesis - S phase
2. genotoxics - cisplatin, doxorubicin - DNA - S phase
3. spindle poisons - taxanes, vinca alkaloids - Microtubules - G2/M

Front 4

Give the name of drug, the molecular target, and the specific cancer used to treat for the following therapies:

1. mAB that recruit immune system
2. mAB that block immune tolerance
3. SMI

Back 4

1. rituxan - targets CD20 on B cells, mAB binding recruits NK cells which induce apopoptic cascade - NHL
1b. herceptin - targets Her2 (EGFR) on cancer cells, mAb binding blocks signaling and induces ADCC - breast cancer
2. yervoy (Ipilimumab) - targets CTL4A on CTL, which prevents CTL4A from binding the B7 ligand on dendritic cells which would normally lead to self-tolerance - melanoma, prostate cancer, lung cancer
3. Gleevac - targets bcr-abl (tyrosine kinase) by competitively inhibiting ATP binding pocket - CML (chronic myelogenous leukemia) and GIST (Gastro-intestinal stromal tumor)
3b. velcade - targets 26s proteasome so that IkB is not degraded, and NFkB (transcrip. factor) is kept in the off state - multiple myeloma, MCL (mantle-cell lymphoma)

Front 5

For Gleevac drug, why is it more effective, in terms of stopping the cancer, to target bcr-abl than Ckit?

Back 5

bcr-abl is a driver of cancer, while Ckit is not a driver.

Front 6

Why doesn't Velcade interfere with degradation of proteins in normal cells and why is this a good targeting strategy?

Back 6

Cancer cells are more sensitive to Velcade than normal cells, because cancer cells produce much more protein than normal cells, so stopping 26S proteasome has a greater effect in cancer cells than normal cells.

This is a good strategy because cancer cells are more reliant on 26S proteasome, since they constantly produce mutated proteins that need to be degraded to keep the cell from build-up of misfolded proteins.

Front 7

Using knowledge of mAB nomenclature, identify the target location, antibody type, and drug type of these mAB:

1. naptumomab
2. cetuximab
3. trastuzumab
4. panitumumab
5. tremelimumab

Back 7

1. tu = tumor, o= mouse, mab = monoclonal antibody
2. tu = tumor, xi = chimeric, mab = mAB
3. tu = tumor, zu = humanized, mab = mAB
4. tu = tumor, u = human, mab = mAB
5. im=immune, u = human, mab = mAB