Antineoplastics V: Signal Transduction Inhibitors - Fitz

Question 1

How are tyrosine kinases important regulators?

Answer 1

Intracellular Signal Trasnduction Pathways in development and multicellular communication

Question 2

Bosutinib, Dasatinib, and Nilotinib were developed to target cells that have become resistant to what?

Answer 2

Imatinib

Question 3

Changes in Target Proteins caused secondary resistance due to what?

Answer 3

Mutation in ATP-binding site that prevents drug binding to the cancer cells (heterogeneity of tumor)

Question 4

What is the only curative therapy for CML?

Answer 4

Bone Marrow Transplant

- Patients over 60 do not qualify and many patients don’t find a donor

Question 5

When the Philadelphia Chromosome was discovered in 1960, what was the standard of treatment for CML?

Answer 5

Busulfan
Hydroxyurea
:: To kill all rapidly dividing cells, leading to a 35-67 month survival rate with 42% hematologic success rate

Question 6

When the BCR-ABL1 gene was discovered, what was the standard of treatment for CML?

Answer 6

Interferon-alpha
:: Decrease cell proliferation, leading to a 55-89 month survival rate with 20-30% cytogenic and 80% hematologic success rate

Question 7

When Tyrosine Kinase Inhibitors were discovered, what was the standard of treatment for CML?

Answer 7

Imatinib
:: Suppress defective enzyme in cancer cells, leading to a more than 5 year survival rate with a 50-95% cytogenic success rate

Question 8

Compare the understanding of the genetic defect for Imatinib and Erlotinib/Geitinib:

Answer 8

Imatinib: Excellent

Erlotinib/Gefitinib: Poor

Question 9

Compare the homogeneity of the disease process among candidate patients (likely responders) for Imatinib and Erlotinib/Geitinib:

Answer 9

Imatinib: Yes, among patients in chronic phase

Erlotinib/Gefitinib: No

Question 10

Compare the uniqueness of drug targets (molecular markers) for Imatinib and Erlotinib/Geitinib:

Answer 10

Imatinib: Only in Cancer Cells

Erlotinib/Gefitinib: In many normal and cancer cells

Question 11

Compare the large scale success for Imatinib and Erlotinib/Geitinib:

Answer 11

Imatinib: Yes

Erlotinib/Gefitinib: Not really (fails more often than it works)