Biologic Drugs

Question 1

Imatinib (MOA, Target, Heme-onc disease, resistance)

Answer 1

MOA: Tyrosine kinase inhibitor. Binds catalytic cleft of ABL on BCR-ABL fusion protein.

Target: ABL catalytic cleft

Disease: CML (t(9;22), Philadelphia chromosome, creates BCR-ABL fusion protein)

Resistance: ABL cleft mutates

Question 2

ATRA (MOA, Target, Heme-onc disease, toxicities)

Answer 2

MOA: Out-competes RAR-PML fusion protein to free RA receptor, allowing normal cellular differentiation

Target: RAR (retinoic acid receptor)

Disease: Acute Promyelocytic Leukemia (APML- AML subset)

Side effects:
-ATRA Syndrome: leukocytosis, capillary leak syndrome (pulmonary edema, respiratory failure), renal failure. Reduce with steroids/chemo

Resistance:

Question 3

Arsenic (MOA, Target, Heme-onc disease, toxicities)

Answer 3

MOA: Same thing as ATRA. Out-competes RAR-PML fusion protein to free RA receptor, allowing normal cellular differentiation

Target: RAR (retinoic acid receptor)

Disease: Acute Promyelocytic Leukemia (APML- AML subset)

Question 4

Rituximab (MOA, Target, Heme-onc disease)

Answer 4

MOA: Chimeric monoclonal antibody vs. CD-20, targeting pre/mature B-cell malignancies via immune activation

Target: CD-20

Disease: NHLs, autoimmune diseases

Question 5

Crizotinib (MOA, Target)

Answer 5

MOA: Tyrosine Kinase Inhibitor

Target: ALK, ROS1, HGFR

Question 6

Thalidomide ((MOA, Heme-onc disease, toxicities)

Answer 6

MOA: Teratogenic in fetus (dont grow arms), but mechanism really cutting off blood supply, good vs. cancer!

Target: unclear

Disease: MM, leprosy

Side effects: teratogenic

Question 7

Trastuzumab ((MOA, Target, Heme-onc disease, toxicities)

Answer 7

MOA: Binds HER-2 receptor, preventing dimerization and pathway oversignaling

Target: HER-2 receptor

Disease: Breast Cancer (20% HER-2+)

Side effects: Cardiac Toxicity

Question 8

Cetuximab (MOA, Target, Heme-onc disease, resistance)

Answer 8

MOA: chimeric monoclonal antibody to EGFR

Target: EGFR (human epidermal growth factor receptor)

Disease: NSCLC

Resistance: K-RAS and BRAF mutations

Question 9

Erlotinib (MOA, Target, disease)

Answer 9

MOA: Tyrosine kinase inhibitor

Target: EGFR (human epidermal growth factor receptor)

Disease: lung, breast, colon cancers

Question 10

Bevacizumab (MOA, Target, Heme-onc disease, toxicities, resistance)

Answer 10

MOA: Inhibits VEGF-R, inhibiting cancer angiogenesis

Target: VEGF-R

Disease:

Side effects:

• hypertension
• pulmonary hemorrhage
• proteinuria
• “financial toxicity”

Resistance:

Question 11

Vemurafinib (MOA, Target, Heme-onc disease, toxicities, resistance)

Answer 11

MOA: RAF inhibitor

Target: V600E BRAF mutation

Disease: NHL, hairy cell leukemia, melanoma, others

Side effects:
-Causes secondary skin cancers

Resistance: BRAF V600E mutations in colon cancer

Question 12

Bortezomib (MOA, Target, Heme-onc disease, toxicities)

Answer 12

MOA: Proteosome inhibitor- proteosome degradation is part of signaling pathway

Target: proteosome

Disease: Multiple myeloma

Side effects:

• Neuropathy
• myelosuppresion

Question 13

Nivolumab (MOA, Target, Heme-onc disease, toxicities, resistance)

Answer 13

MOA: tumors bind PD-1 receptor on T-cells inactivating them to prevent it targeting tumor. Nivolumab binds PD-1 receptor to block tumor deactivation of T-cells

Target: PD-1 receptor

Disease: HL, lots of other non-H/O

Side effects:

• Immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies
• Fatigue
• Rash/pruritis
• Musculoskeletal pain

Resistance: