Targeted Therapy And Biologics (Fitz)

Question 1

Name the Bcr-Abl tyrosine kinase inhibitors

Answer 1

Imatinib
Dasatinib

BCR-ABL –> CML

Question 2

How does Imatinib inhibit transfer of phosphate to Tyr on substrates?

Answer 2

Occupies ATP cofactor binding site on BCR-ABL oncogene

Question 3

Indication for Dasatinib?

Answer 3

Primary and imatinib resistant CML

Question 4

Tyrosine kinase targets of Imatinib? Therapeutic use?

Answer 4

BCR-Abl, c-Kit, PDGFR

CML, GIST

Question 5

Tyrosine kinase target of Dasatinib? Therapeutic use?

Answer 5

Bcr-Abl, Src family

Imatinib-resistant CML, ALL with Philadelphia Chromsome

Question 6

What oncogenic form of RTK is found in GIST and what tyrosine kinase inhibitor can be used?

Answer 6

KIT or PDGFR-alpha

Imatinib
Imatinib-resistant GIST –> Sunitinib

Question 7

Adverse effects of Imatinib?

Answer 7

Many drug interaction d/t hepatic CYP450-rifampin and st johns wort induce CYP450 and hasten clearance of imatinib

Question 8

Gefitinib, Erlotinib, Lapatinib, Sunitinib, and Sorafenib are what type of RTK inhibitors?

Answer 8

Membrane-associated

Question 9

This drug targets HER2 and EGFR

Answer 9

Lapatinib

Breast cancer

Question 10

These drugs target EGFR only

Answer 10

Gefitinib
Erlotinib

NSCLC

Question 11

These drugs target PDGFR and VEGFR

Answer 11

Sunitinib (also c-kit) –> GIFT and RCC

Sorafenib (also inhibits RAF) –> RCC and HCC

Question 12

This drug specifically inhibits mutant BRAF V600E

Answer 12

Vemurafenib

Raf=serine/threonine kinase

Question 13

Therapeutic use of Venurafenib?

Answer 13

Metastatic malignant melanoma

Graph on slide 28

Question 14

Name the antibody drugs target EGFR receptor and their therapeutic uses

Answer 14

Cetuximab-colorectal; head and neck (tumors with KRAS mutation unresponsive)

Panitumumab-Colorectal cancer (except KRAS mutations)

Question 15

Name the antibody drug that targets HER2 receptor and therapeutic use

Answer 15

Trastuzumab-HER2+ breast cancer

Question 16

Name the antibody drug that targets VEGF ligand and therapeutic use

Answer 16

Bevacizumab-RCC (add to chemo for colon, lung, head, and neck)

Question 17

___ is a determinant of the clinical response to EGFR inhibition

Answer 17

Ras

Question 18

Name the angiogenesis drug(s) for:

Antibody-____

RTK inhibitors-____

Answer 18

Antibody=Bevacizumab –> targets VEGF

RTK inhibitors=Sunitinib and sorafenib

Question 19

Risks in women taking Bevacizumab for metastatic breast cancer?

Answer 19

Severe high BP
Bleeding
Heart attack or heart failure

Question 20

RCC responds to angiogenesis inhibitors because it is a highly vascular tumor dependent on __ and receptor __ for pathogenesis

Answer 20

VEGF, PDGF

cognate RTKs

Question 21

This antibody drug is for CD20+ B cell lymphoma (NHL and B-CLL)

Answer 21

Rituxomab-anti-CD20