Lecture 8 - Additional Agents

Question 1

Emerging area in cancer therapeutics

Answer 1

chromatin modifications

Question 2

Chromatin regulation

Answer 2

acetylation of histones can increase transcription of tumor suppressor genes

Question 3

Methylation

Answer 3

methylation at histone 3, lysine 27 by EZH2 is increased in many cancers
EZH2 methylates lysines and turns off genes

Question 4

Gene swithced on when

Answer 4

unmethylated cytosines
acetylated histones

Question 5

Gene switched off when

Answer 5

methylated cytosines
deacetylated histones

Question 6

DNA methyl transferase inhibitor

Answer 6

5-azacytosine
enzyme can’t put methyl group on N

Question 7

5-azacytosine

Answer 7

incorporates into DNA and covalently binds DNMT enzymes preventing their function
DNMT inhibitors result in reactivation of tumor suppressor genes
for myelodysplatic syndrome

Question 8

Targeting proteasome

Answer 8

proteasome breaks down misfolded proteins and proteins get targeting for degradation by ubiquitination
multiple myeloma cells are good targets for proteasome inhibition because they make a lot of proteins

Question 9

Proteasome inhibitor

Answer 9

bortezomib

Question 10

Bortezomib

Answer 10

inhibit proteasome activity
26S proteasome degrades ubiquinated proteins
treatment of multiple myeloma

Question 11

Pomalidomide

Answer 11

for treating multiple myeloma and kaposi sarcoma - degrades transcription factors important in these cancers
binds cereblon to induce it to ubiquitinate and degrade IKZF TFs which are important in lympocyte development and regulate cell survival in multiple myeloma
regulated by POMALYST and REMS; requires certification to be prescribed/dispensed

Question 12

Venetoclax

Answer 12

prevents inhibition of BCL-2, an anti-apoptotic protein, inhibits anti-apoptotic protein –> drives cell death via apoptosis
small molecule that inhibits protein-protein interaction!
approved for CLL and used in combo with azacitidine for AML