Molecular Anticancer

Question 1

mainstay therapy for CML?

Answer 1

tyrosine kinase inhibitors

Question 2

Imatinib

1. MOA?
2. PEARLS?
3. major side effects?

Answer 2

1. blocks Bcr-Abl’s ability to phosphorylate and activate proteins
2. first line therapy for CML
3. hepatotoxicity, GI bleeding, tumor lysis syndrome

Question 3

Nilotinib

1. MOA?
2. uses?
3. major side effects?

Answer 3

1. similar to Imatinib
2. used in Bcr-Abl mutants resistant against Imatinib but ineffective against T315I (CML)
3. myelosuppression

Question 4

Dastinib

1. MOA?
2. uses?
3. major side effects?

Answer 4

1. similar to Imatinib
2. used in Bcr-Abl mutants resistant to Imatinib but ineffective against T315I (CML)
3. myelosuppression, pulmonary arterial hypertension

Question 5

Bosutinib

1. MOA?
2. uses?
3. major side effects?

Answer 5

second line for CML

1. ATP competitive inhibitor of Bcr-Abl
2. at strains resistant or tolerant to first line therapy
3. GI toxicity, hepatic toxicity, renal toxicity

Question 6

Ponatinib

1. MOA?
2. PEARLS?
3. major side effects?

Answer 6

second line therapy for CML

effective against T315I mutant!

boxed warning!

Question 7

four types of melanoma?

Answer 7

1. cutaneous
2. acral
3. mucosal
4. uveal

Question 8

BRAF mutations encode ______

most common mutation?
second most common?

Answer 8

serine threonine kinase

1. BRAFV600E
2. BRAFV600K

Question 9

Vemurafenib

1. MOA?
2. uses?
3. major side effects?
4. contraindications?

Answer 9

1. inhibits BRAF kinase
2. unresectabe stage III or IV metastatic melanoma w/ BRAFV600 mutations
3. new primary cutaneous melanoma, QT prolongation
4. cannot be used in melanomas with wild-type BRAF mutation

Question 10

Dabrafenib

1. uses?
2. major side effects?
3. contraindications?

Answer 10

1. unresectabe stage III or IV metastatic melanoma w/ BRAFV600 mutations
2. serious febrile fever rxns; hypotension, rigors/chills, dehydration, kidney failure
3. cannot be used in melanomas with wild-type BRAF mutation

Question 11

Trametinib

1. MOA?
2. major side effects?
3. contraindications?

Answer 11

1. inhibits MEK which is an extracellular signal/regulated kinase
2. serious skin toxicity, retinal vein occlusion
3. cannot be used in melanomas with wild-type BRAF mutation

Question 12

which epidermal growth factor receptor (EGFR) is overexpresed in breast, ovarian, and gastric cancers?

Answer 12

ErbB2/her2/neu

Question 13

types of non-small cell lung cancers?

Answer 13

squamous cell, adenocarcinoma, large-cell

Question 14

first-line treatment options are use for tumors for which exon mutations in the EGFR?

MOA?

Answer 14

1. exon 19 deletion
2. exon 21 (L858R) mutation

MOA = inhibit kinase function of EGFR and inhibition of downstream signaling

Question 15

Erlotinib

1. class?
2. side effects?
3. drug interactions?

Answer 15

1. EGFR-inhibitor
2. N/V, interstitial lung disease
3. drugs that target CYP3A4, proton pump inhibitors, warfarin

Question 16

Gefitinib

1. class?
2. side effects?

Answer 16

1. EGFR-inhibitor

2. interstitial lung disease, liver damage, GI perforation

Question 17

Afatinib

1. class?
2. side effects?

Answer 17

1. EGFR-inhibitor

2. N/V, rash, fatigue, pulmonary toxicity

Question 18

1. drug target in Anaplastic large cell lymphoma?

2. what fusion product becomes constitutively active?

Answer 18

1. ALK - cell surface receptor tyrosine kinase

2. fusion between EML4+ALK genes at Ch2 become constitutively active

Question 19

Crizotinib

1. class?
2. uses?
3. side effects?

Answer 19

1. ATP-competitive inhibitor of ALK
2. ALK (+) metastatic NSCLC (oral use)
3. visual disorders, N/V, pulmonary embolism

Question 20

Ceritinib

1. class?
2. uses?
3. side effects?

Answer 20

1. ALK inhibitor
2. oral Tx for ALK(+) metastatic NSCLC progressed on Crizotinib or intolerant patients
3. N/V, elevated liver enzymes, QT prolongation

Question 21

Trastuzumab

1. class?
2. MOA?
3. uses?
4. side effects?

Answer 21

1. Anti-ErbB2 humanized monoclonal
2. prevents transduction of proliferation & survival signals, eventual degradation of the receptor
3. node (+) or (-) breast cancer that includes ErbB2 (part of combo) and metastatic breast cancer (part of combo)
4. Boxed warning - cardiomyopathy, infusion rxns, pulmonary toxicity

Question 22

Pertuzumab

1. class?
2. MOA?
3. uses?
4. side effects?

Answer 22

1. Anti-ErbB2 humanized monoclonal
2. prevents ErbB2 interaction which inhibits proliferation signals
3. in combo therapy for ErbB2 (+) breast cancer with no history of anti-ErbB2 therapy

or in neoadjuvant setting with Trastuzumab + docetaxel for treatment of early breast cancer

4. LV dysfunction, CHF, embryo-fetal toxicity, allergic reaction

Question 23

Nivolumab

1. class?
2. uses?
3. side effects?

Answer 23

1. humanized monoclonal antibody that inhibits PD1
2. unrectable or mestastatic melanoma in combo w/ ipilimumab for BRAF wild-type tumors

advanced/metastatic squamous NSCLC that has progressed on platinum-based therpay

3. rash, N/V, constipation, severe immune mediated side effects

Question 24

Pembrolizumab

1. class?
2. uses?
3. side effects?

Answer 24

1. humanized monoclonal antibody that inhibits PD1
2. 1st line therapy for advanced NSCLC that has increased expression of PD-L1 but no EGFR or ALK mutatnts, no history of previous chemo

malignancies with microsatellite instability or mismatch repair deficiencies

colorectal cancers that have progressed on previous therapies

second line for advanced NSCLC that have progressed on platinum-based therapy

advanced urothelial bladder cancers

3. pneumonitis, colitis, endocrinopathies, nephritis, renal failure, hepatitis, complications of stem cell transplant