Examples of targeted therapy Flashcards
Chronic myeloid leukaemia
With Philadelphia chromsome [t(9;22) translocation], form abnormal fusion protein bcr-abl and self-sufficiency of growth signals. Accumulation of myeloid leukaemia in blood and bone marrow
Target bcr-abl (abnormal fusion protein with tyrosine kinase activity)
Use imatinib (gleveec) - small molecular drug
No adverse effect
Imatinib inhibits bcr-abl tyrosine kinase in chronic myeloid leukaemia and c-kit tyrosine kinase in GI stromal tumours. It binds to their ATP binding site.
Non-small cell lung cancer
With self-sufficiency in growth signals by somatic mutation of ras or EGFR (human epidermal growth factor receptor-1)
Target mutant EGFR (point mutations, deletions, gene amplification)
Use gefitinib - small molecular drug
Adverse effect: mechanism-based skin and GI toxicities
Gefitinib binds to ATP binding site of EGFR, inhibits EGFR tyrosine kinase activity
Breast cancer
With self-sufficiency in growth signals by genetic amplification of HER-2 (human epidermal growth factor receptor-2)
Target Her-2
Use trastuzumab (Herceptin) - recombinant humanised monoclonal antibody
Adverse effect: infusion reactions - hypersensitive reactions - pruritus, urticaria, fever, rigors/chills, diaphoresis, bronchospasms, and cardiovascular collapse
Trastuzumab/Herceptin binds to extracellular domain of HER2, blocks binding of epidermal growth factor to HER2, stop the growing of tumour cells
Renal cell carcinoma
Most common form of kidney cancer. With sustained angiogenesis through mutation of von Hippel Lindau tumour suppressor gene
Target VEGF
Use sunitinib - small molecular drug
Adverse effect: hypertension, haemorrhage, cardiac failure
Central role of von Hippel Lindau protein - transcriptional regulation of angiogenic factors
Sunitinib inhibits vascular endothelial growth factor and platelet-derived growth factor receptors by binding to their ATP-binding sites, inhibiting receptor tyrosine kinase activity
