clinical: Targeted therapies

Question 1

Target therapies can be Mabs or Ibs. What are each?

Answer 1

Mabs are monoclonal antibodies

Ibs are signal transduction inhibitors

Question 2

Myeleproliferative disorders tend to have a mutation that cause what?

Answer 2

Constitutively active tyrosine kinase receptor

Question 3

Pathophysiology of CML: fusion of what two regions of which chromosomes renders the tyrosine kinase constitutively active

Answer 3

Break point cluster region (BCR) and Ableson Oncogene product (Abl)

Question 4

What is a proteosome?

Answer 4

Enzyme complexes present in both healthy and cancerous cells. Proteasomes degrade intracellular proteins in a regulated manner

Question 5

Imatinib is a signal transduction inhibitor that binds where?

Answer 5

Binds the ATP binding domain of the Abl kinase preventing substrate phosphorylation and signaling preventing downstream signaling

Question 6

MOA of Ruxolitinib and indicated for tx of what disease that causes erythrocytosis

Answer 6

Block cytokine signaling and amplified cytokine and growth factor expression, effectively a JAK2 inhibitor and used for tx of Polycythemia Vera

Question 7

MOA of Ibrutinib and indicated for tx of what disease that causes high levels of IgM in the blood leading to hyperviscosity and is associated with lymphoplasmacytic lymphoma

Answer 7

BTK inhibitor in b-cell receptor signaling used to treat Waldenstrom macroglobulinemia

CYP3A4 (lots of drug drug interactions) and can also be used for mantle cell lymphoma

Question 8

Idelalisib inhibits what part of the BCR cascade?

Answer 8

P13K 2nd messenger used for tx of CLL or relapsed follicular B cell non-hodgkins lymphoma of FL/relapsed SLL

Question 9

bortezomib is a _______inhibitor

Answer 9

26s proteosome inhibitor

Question 10

the Abl ATP biniding domain mutates and can become resistant to imatinib. What other treatments are there if this happens in a pt with CML?

Answer 10

Dasatinib or Nilotinib

Question 11

Imatinib adverse effects

Answer 11

edema, hepatotoxic

Question 12

What are some potentially fatal adverse effects of idelalisib (P13K inhibitor that treats relapses CLL/SLL, Relapsed follicular B-Cell NHL)

Answer 12

Fatal hepatoxicity

Intestinal Perforation

Question 13

Idelalisib can have many drug drug interactions because

Answer 13

it’s a CYP3A4 inhibitor

Question 14

Alemtuzumab (campath) is directed against CD

Answer 14

CD52