Targeted cancer treatment Flashcards
Bevacizumab
Anti-VEGFA monoclonal antibody, neutralising VEGFA
Increases cardiovascular risk
Ramucirumab
IgG1 monoclonal antibody against the extracellular domain of the VEGFR2 receptor
Increases circulating VEGF levels - may be an issue
Small molecular inhibitors
Target the catalytic domain of RTKs
Sorafenib - inhibit VEGFRs, c-Raf, B-Raf and PDGFRs
Axitinib - more selectivity for VEGFR2 and improved potency
Efficacy limited by development of resistance and toxicity
Consequences of VEGF inhibition
Hypertension - VEGFR2 normally generates the vasodilators NO and PGI2
Thromboembolic events (cardiac/cerebral ischemia) - VEGF normally prevents adherence of platelets to vasculature and maintains endothelial cell survival
Heart failure - VEGF normally maintains cardiomyocyte survival
VEGF normally interacts with ECs, platelets and the coagulation cascade - inhibition causes poor wound healing
Removal of VEGF from podocytes in the renal system causes cell loss and proteinuria
Trastuzumab
Monoclonal antibody against the extracellular domain of HER2, used for breast cancer
HER2 is overexpressed in cancers and causes tumour development and angiogenesis
Treatment associated with cardiac toxicity
Tamoxifen
Oestrogen receptor antagonist, used as 5-year therapy in postmenopausal women with ER+ breast cancer following surgery
Use limited to 5 years as long-term use increases risk of endometrial cancer
Side effects: nausea/vomiting, hot flashes, fatigue, mood swings, vaginal bleeding/dryness
CAR-T cell therapy
Patient’s T-cells are collected and engineered to express artificial receptors for a specific tumour antigen
Used for haematologic cancers, reduces remission by 80%
Vaccines
HPV causes 70% of cervical cancers
Quadrivalen (Gerdasil) and bivalent (Cervarix) vaccines available
Gerdasil side-effects are mild and include headache, diziness, sore muscles, raised temperature, nausea, diarrhoea, stomach pain, itching and rash
