Novel Cancer Therapies

Question 1

imatinib mesylate - indication and oncogene target

Answer 1

CML

Bcr-abl chromosomal translocation

Question 2

erlotinib, cetuximab, panitumumab, gefitinib - indication and oncogene target

Answer 2

oncogene: epidermal growth factor receptor overexpression/activation
tumor type: non-small cell lung cancer, colorectal metastatic disease, breast cancer

Question 3

trastuzumab - indication and oncogene target

Answer 3

indication: breast cancer
MOA: Her2/neu overexpression

Question 4

imatinib mesylate brand name

Answer 4

Gleevac

Question 5

imatinib mesylate MOA

Answer 5

tyrosine kinase inhibitor of Bcr-Abl fusion protein in CML

also inhibtis PDGR, stem cell factor, c-kit

Question 6

imatinib mesylate - use in GI tumors

Answer 6

blocks overexpression of c-kit tyrosine kinase receptor in GIST

Question 7

ADR of imatinib and interactions

Answer 7

cardiac toxicity

interactions w/ inhibitors of CYP3A4

Question 8

trastuzumab MOA

Answer 8

Anti-Her2/Neu Ab - blocks HER2/neu receptor from growth factor binding

Question 9

trastuzumab ADRs and interactions

Answer 9

cardiac tox, dyspnea

allergic rxns

Question 10

erlotinib (tarceva) MOA

Answer 10

small molecule EGFR inhibitor active against lung and pancreatic cancers (w/ activating mutation of EGFR receptors)

Question 11

erlotinib ADRs and interactions

Answer 11

rash diarrhea dyspnea

interactions: smoking, CYP3A4 inhibitors

Question 12

why are anti-angiogenic factors promising?

Answer 12

resistance is infrequent
activity does not depend on tumor cell targeting
chronic therapy could prevent vascularization of tumors

Question 13

bevacizumab (avastin) MOA and indications

Answer 13

anti-VEGF (mAb) - blocks angiogenic actions

colon and lung cancer, macular degeneration and retinal diseases

Question 14

ADR of bevacizumab

Answer 14

bleeding

Question 15

Vemurafenib (zelboraf) MOA and indications

Answer 15

BRAF serine-threonine kinase (protein kinase) inhibitor

metastatic melanoma w/ V600E BRAF mutations

Question 16

intrinsic resistance

Answer 16

tumor displays resistance to chemo right from the onset of tx

Question 17

extrinsic resistance

Answer 17

tumor is initially sensitive, but then commences regrowth despite ongoing tx

Question 18

enhanced drug efflux is assoc w/ what kind of mutation?

Answer 18

ATP-binding casette (ABC) transporters

• P-glycoprotein
• multi drug resistance protein (MRP1)
• ABCG2

Question 19

list the drugs that are effluxed in overexpression of P-glycoprotein

Answer 19

see list on paper

Question 20

if overexpression of efflux protein is confirmed, don’t use….

Answer 20

because they will be effluxed

see list on paper

Question 21

other mechanisms for multi drug resistance

Answer 21

decreased topoisomerase II expression
increased DNA repair
GST
failure to induce apoptosis

Question 22

collateral sensitivity

Answer 22

when resistance to one drug results in biochem changes that make the cell more sensitive to a second drug

Question 23

genomic instability - importance in drug resistance

Answer 23

increased likelihood that mutations leading to drug resistance will occur early in life of tumor

Question 24

multiple drug resistance

Answer 24

cancers become resistant to diverse chemo after exposure to a single agent