Targeted cancer therapies

Question 1

Protein kinase inhibitors include

Answer 1

imatinib (gleevec)

Question 2

Imatinib MoA

Answer 2

binds to a segment of the kinase domain, stabilizing it in the active formation. Prevents ATP binding

Question 3

Imatinib mechanism of resistance

Answer 3

mutations of kinase domain

Question 4

Imatinib toxicity

Answer 4

GI distress, edema, hepatotoxicity, myelosuppression

Question 5

What receptor does Imatinib have inhibitory activity against?

Answer 5

PDGFR - platelet derived growth factor receptor, as well as tyrosine kinasees

Question 6

Which cancers is Imatinib considered effective in treating?

Answer 6

chronic myelogenous leukemia, gastrointestinal stromal tumors, chronic myelomonocytic leukemia, hypereosiniphilic syndrome

Question 7

Histone Deacetylase Inhibitors (HDAC) include

Answer 7

Vorinostat and Romidepsin

Question 8

HDAC mechanism of action

Answer 8

Regulate gene transcription by correcting the balance between acetylated and deacetylated histones in tumor cells. Bind to the active side of HDACs, resulting in inhibition of enzymatic activity

Question 9

HDAC mechanism of resistance

Answer 9

none

Question 10

Toxicity HDACs

Answer 10

Specific to Vorinistat: fatigue, nausea, thrombocytopenia, QTc prolongation

Question 11

Vorinistat and Romidepsin are used for

Answer 11

cutaneous T-cell lymphoma

Question 12

Monoclonal antibodies include

Answer 12

Cetuximab (Erbitux)

Question 13

Cetuximab MoA

Answer 13

binds to the domain of EGFR and causes downregulation of its expression, and induction of antibody-dependent cell mediated cytotoxicity against the tumor cells

Question 14

Mechanism of resistance - Cetuximab

Answer 14

mutations in tumores (oncogene K-ras)

Question 15

Toxicities - Cetuximab

Answer 15

Rash, itchiness, nail changes, diarrhea, allergic rxn

Question 16

How is cetuximab administered?

Answer 16

IV for treatment of solid skin tumors