TKIs Summing Them up. Higher Yeild.

Question 1

What is the General way that Tyrosine kinase Inhibitors prevent act to inhibit, what is the exception?
- what is the common mechanism of Resistance?

Answer 1

MOA:

• They bind to the ATP binding site inhibiting TK action
• Bortezomib is excluded from this

MOR:

• Altered ATP binding site that affects drug binding but doesn’t affect TK activity
• This shifts dose-response curve right
• Pushes Dose needed outside of therapeutic Window

Question 2

T or F: Tyrosine Kinase Inhibitors are metabolized by Cytochrome p-450.

Answer 2

True, this means we can see a lot of Drug-Drug Interactions with these

Question 3

What is the only Tyrosine Kinase Inhibitor that is not given orally?

• what major side effect can it have?
• MOA?

Answer 3

Bortezomib

• Cardiac Side effects can be caused

MOA:

• Blocks Degredation of IkB-alpha by 26-S proteosome, keeping NFkB from translocating into the nucleus
• Creates increased pro-apoptotic and Decreased anti-apoptotic signals

Question 4

What Tyrosine Kinase Inhibitors cause Thyroid Toxicity?

• What is their target?
• Cancer targeted

Answer 4

• Imatinib
• Nilotinib
• Dasatinib

Target - BCR-ABL

Cancer:

• Chronic Myelogenic Leukemia (CML)
• Acute Lymphoblastic Leukemia

Question 5

What Tyrosine Kinase Inhibitors work on VEGF?

- cancers targeted?

Answer 5

• Sunitinib - GIST
• Sorafenib - Hepatocellular Carcinoma
• Pazopanib - Soft Tissue Carcinoma

Question 6

What Tyrosine Kinase Inhibitors work on EGFR?

- Cancers targeted?

Answer 6

• Erlotinib
• Gefitinib
• Lapatinib - Pancreatic Cancer
• Lung, Breast all