RTKs Flashcards
What about non-RTKs?
Equally important and involved in different cancers.
Difficult to distinguish - lot of functional merging.
Why is imatinib so powerful and how does this relate to it being a small molecule?
Blocks several other kinases.
Due to structural similarity between TK domains, small molecule inhibitors inhibit several different RTKs.
How does Cetuximab inhibit EGFR?
Downregulation, inhibition of cell division, apoptotic induction, decreased VEGF, decreased MMP, ADCC mediation in vitro.
How has perception been modified?
cDNA re-engineered so constant regions composed of human sequence –> humanised anti-HER2 not immunogenic and remains functional for up to 1 month.
What evidence suggests herceptin may use ADCC to kill cells?
Immunocompromised mice with FcY receptor gene deletion –> reduced ability for Herceptin mediated cell killing.
Do we have more monoclonal Abs or small molecule inhibitors?
Fewer monoclonal Abs as larger and more difficult to develop.
Why do we need predictive or prognostic biomarkers?
Save patients from unnecessary toxicity.
Control medical cost.
Improve success rate of clinical drug development.
What condition has Cetuximab shown efficacy for?
How can we predict response?
Head and neck cancer in combo with chemo / EGFR expressing, ET Kras CRC in combo with chemo or irinotecan.
Rash predicts good response –> immune response stimulation?
What are the properties of mutant EGFR lung cancer?
Enhanced inhibition by TKI.
Signalling through ErbB3 survival pathways (Art)
Oncogene addiction.
