Chapter 39: Cancer Signal Transduction

Question 1

What kind of tumor expression predicts the effectiveness of EGFR and HER2/neu inhibitors?

Answer 1

KRAS mutation

Question 2

What drug reversibly inhibits EGFR (ErbB1) tyrosine kinase domain, competing with ATP binding, and treats non-small cell lung cancer, but is more favorable in women/nonsmokers/bronchoalveolar cell carcinoma?

Answer 2

gefitinib

Question 3

What drug reversibly inhibits EGFR (ErbB1) tyrosine kinase domain, competing with ATP binding, and treats non-small cell lung cancer, pancreatic carcinoma, and certain glioblastomas? It has a greater survival benefit than its predecessor.

Answer 3

erlotinib

Question 4

What drug is a monoclonal antibody that binds to EGFR (ErbB1) and treats colorectal and head & neck cancer/? It works best in combo with irinotecan.

Answer 4

cetuximab

Question 5

What mouse/human monoclonal antibody against ErbB2 (HER2) treats breast cancer but causes cardiotoxicity with anthracyclines?

Answer 5

trastuzumab

Question 6

What is a reversible inhibitor of both EGFR and ErbB2 to treat breast cancer, and crosses the BBB so is good with brain metastases?

Answer 6

lapatinib

Question 7

What 2 drugs do people with T790M mutation develop resistance to, and what OTHER drug is better acting with this mutation?

Answer 7

gefitinib, erlotinib.

Better: lapatinib

Question 8

The farnesyltransferase inhibitors tipifarnib and lonafarnib are used for what cancer mutation?

Answer 8

RAS

Question 9

What drug treats CML by inhibiting ABL, GIST expressing CD117 by inhibiting KIT, and idiopathetic hypereosinophilic syndrome by inhibiting PDGFR?

Answer 9

imatinib

Question 10

What 2 drugs are an improvement over imatinib because they can bind the activation loop anytime (not just when it’s closed), and have greater efficacy against wild-type BCR-ABL, inhibting all forms except T315I?

Answer 10

dasatinib, nilotinib

Question 11

What treats melanoma by inhibiting B-RAF and RCC, HCC by inhibiting VEGFR-2, PDGFR-beta?

Answer 11

sorafenib (has ‘RAF’ in name)

Question 12

What binds to FKBP12, creating a complex that binds to mTOR, inhibiting translation? It is used for immunosuppression.

Answer 12

rapamycin

Question 13

What are analogues of rapamycin that inhibit mTOR and treat RCC? They cause rash and mucositis.

Answer 13

temsirolimus, everolimus

Question 14

What inhibits an active site N terminal threonine residue within a 20S subunit of a proteosome, and also may inhibit NF-kB thru IKF stabilization OR misfolding proteins –> cell death?

Answer 14

bortezomib

Question 15

What is bortezomib used to treat? Side effects?

Answer 15

multiple myeloma

- neutropenia, thrombocytopenia, neuropathy

Question 16

What is a monoclonal IgG1 antibody against VEGF-A, increasing hypoxia? It improves drug delivery by increasing vascular permeability, leading to increased interstitial fluid pressure in the tumor.

Answer 16

bevacizumab

Question 17

What angiogenesis inhibitor treats metastatic colorectal cancer and non-small cell lung cancer (in combo with carboplatin, paclitaxel)?

Answer 17

bevacizumab

Question 18

What angiogenesis inhibitor causes side effects of thromboembolism, proteinuria, HTN, impaired wound healing, and gastrointestinal perforation?

Answer 18

bevacizumab

Question 19

What inhibits VEGFR-1, VEGFR-2 and PDGFR, and is used to treat RCC?

Answer 19

sunitinib

Question 20

What inhibits VEGFR-1, VEGFR-2, PDGFR, AND BRAF, and is used to treat RCC?

Answer 20

sorefenib

Question 21

What inhibits VEGFR-1, VEGFR-2, EGFR, AND RET, and is being tested for non small cell lung carcinoma?

Answer 21

vandetanib

Question 22

What is a glutamic acid derivative that causes side effects of thrombotic disorder, peripheral neuropathy, constipation, somnolence, phocomelia in infants and is highly contraindicated in pregnancy?

Answer 22

thalidomide

phocomelia = stunted limb development

Question 23

What is an immunomodulatory drug that inhibits bFGF and TNF-alpha, and costimulates T cells, and is used to treat multiple myeloma and erythema nodosum leprosum?

Answer 23

thalidomide

Question 24

What should thalidomide be used in combination with to treat muliple myeloma?

Answer 24

dexamethasone

Question 25

What is a thalidomide analogue (with enhanced action & less side effects) used to treat multiple myeloma and myelodysplastic syndrome with 5q deletion?

Answer 25

lenalidomide

Question 26

What are the anti-CD20 analogues?

Answer 26

rituximab, tositumomab, ibritumomab

Question 27

What do rituximab, tositumomab, and ibritumomab treat?

Answer 27

all 3: B cell non-Hodgkin’s lymphoma

tositumomab and ibritumomab: refractory disease and stem cell implant

Question 28

What is the anti-CD52 analogue and what does it treat?

Answer 28

alemtuzumab: CLL & stem cell transplant

Question 29

What is the fusion protein of diptheria toxin and OL-2 that targets CD25 and IL-2?

Answer 29

denileukin diftitox

Question 30

What does denileukin diftitox treat?

Answer 30

T cell non-Hodgkin’s lymphoma

Question 31

What is a conjugate of an anti-CD33 antibody and calicheamicin

Answer 31

gemtuzumab

Question 32

What does gemtuzumab treat?

Answer 32

AML

Question 33

What is the main side effect common in tumor-specific monoclonal antibodies, and which one has the worst ones?

Answer 33

immunosupression

alemtuzumab has worst, with bacterial fungal, and viral infections including P. jiroveci, b/c it kills both B & T cells