Chapter 39: Cancer Signal Transduction Flashcards
What kind of tumor expression predicts the effectiveness of EGFR and HER2/neu inhibitors?
KRAS mutation
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?
gefitinib
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.
erlotinib
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.
cetuximab
What mouse/human monoclonal antibody against ErbB2 (HER2) treats breast cancer but causes cardiotoxicity with anthracyclines?
trastuzumab
What is a reversible inhibitor of both EGFR and ErbB2 to treat breast cancer, and crosses the BBB so is good with brain metastases?
lapatinib
What 2 drugs do people with T790M mutation develop resistance to, and what OTHER drug is better acting with this mutation?
gefitinib, erlotinib.
Better: lapatinib
The farnesyltransferase inhibitors tipifarnib and lonafarnib are used for what cancer mutation?
RAS
What drug treats CML by inhibiting ABL, GIST expressing CD117 by inhibiting KIT, and idiopathetic hypereosinophilic syndrome by inhibiting PDGFR?
imatinib
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?
dasatinib, nilotinib
What treats melanoma by inhibiting B-RAF and RCC, HCC by inhibiting VEGFR-2, PDGFR-beta?
sorafenib (has ‘RAF’ in name)
What binds to FKBP12, creating a complex that binds to mTOR, inhibiting translation? It is used for immunosuppression.
rapamycin
What are analogues of rapamycin that inhibit mTOR and treat RCC? They cause rash and mucositis.
temsirolimus, everolimus
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?
bortezomib
What is bortezomib used to treat? Side effects?
multiple myeloma
- neutropenia, thrombocytopenia, neuropathy
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.
bevacizumab
What angiogenesis inhibitor treats metastatic colorectal cancer and non-small cell lung cancer (in combo with carboplatin, paclitaxel)?
bevacizumab
What angiogenesis inhibitor causes side effects of thromboembolism, proteinuria, HTN, impaired wound healing, and gastrointestinal perforation?
bevacizumab
What inhibits VEGFR-1, VEGFR-2 and PDGFR, and is used to treat RCC?
sunitinib
What inhibits VEGFR-1, VEGFR-2, PDGFR, AND BRAF, and is used to treat RCC?
sorefenib
What inhibits VEGFR-1, VEGFR-2, EGFR, AND RET, and is being tested for non small cell lung carcinoma?
vandetanib
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?
thalidomide
phocomelia = stunted limb development
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?
thalidomide
What should thalidomide be used in combination with to treat muliple myeloma?
dexamethasone
What is a thalidomide analogue (with enhanced action & less side effects) used to treat multiple myeloma and myelodysplastic syndrome with 5q deletion?
lenalidomide
What are the anti-CD20 analogues?
rituximab, tositumomab, ibritumomab
What do rituximab, tositumomab, and ibritumomab treat?
all 3: B cell non-Hodgkin’s lymphoma
tositumomab and ibritumomab: refractory disease and stem cell implant
What is the anti-CD52 analogue and what does it treat?
alemtuzumab: CLL & stem cell transplant
What is the fusion protein of diptheria toxin and OL-2 that targets CD25 and IL-2?
denileukin diftitox
What does denileukin diftitox treat?
T cell non-Hodgkin’s lymphoma
What is a conjugate of an anti-CD33 antibody and calicheamicin
gemtuzumab
What does gemtuzumab treat?
AML
What is the main side effect common in tumor-specific monoclonal antibodies, and which one has the worst ones?
immunosupression
alemtuzumab has worst, with bacterial fungal, and viral infections including P. jiroveci, b/c it kills both B & T cells
