Targeted agents Flashcards
What do these agents target?
Mutant or over-expressed proteins, rather than the normal mechanisms of cell division
What are monoclonal antibodies and how are they given?
Modified human antibodies. All given as IV infusions
Herceptin?
Also known as Trastuzumab, it is a monoclonal antibody against HER2.
Used adjuvantly in breast cancer, and for metastatic treatment of patients with HER2+ disease
What is Ipilimumab? How does it work?
Ipilimumab is an anti-CTLA4 monoclonal antibody that blocks regulatory immune function - releasing effective anti-tumour immunity for a small but important group of patients who can achieve durable responses/ remissions
What cancer is Ipilimumab licensed for?
Metastatic melanoma
What are tyrosine kinase inhibitors?
(end in -ib). These are usually oral drugs with a once or twice dialy dosing. They are metabolised by the CYP pathways in the liver, so drug interactions can be a problem
What is Sunitinib?
An Anti-VEGFR multi-targeted oral tyrosine kinase inhibitor, which can block cell growth factors and angiogenesis
What is Sunitinib used for?
Palliative treatment of renal cell cancer, pancreatic neuroendocrine tumours and GI stromal tumours
What is erlotinib?
An anti-EGFR (endothelial growth factor receptor) tyrosine kinase inhibitor
When is erlotinib indicated in treatment?
Non-small cell lung cancer with evidence of relevant EGFR activating mutations
What is Vemurafenib?
It blocks the pathway of mutant BRAF genes, that normally lead to activation of kinase signalling pathways, with a role in cell proliferation, migration and apoptosis (RAS/ RAF/ MAPK). The blockage can result in dramatic responses but further mutations drive the development of drug resistant clones
When is Vemurafenib indicated?
It is effective palliative therapy for patients with V600E BRAF mutation metastatic melanoma.
What is Everolimus?
Everolimus is a mTor inhibitor (ends in -us), available orally.
It is an oral serine/ threonine kinase inhibitor clumsily named mTor (mammalian target of rapamycin), which is part of the P13K/AKt/mTor intracellular signalling pathway important in apoptosis.
When is Everolimus indicated?
Palliative treatment of renal cell carcinoma, and in combination with exemestane, in ER+ HER2- metastatic breast cancer.
Most effective in patients with very rate tuberous sclerosis complex
Why are targeted therapies often dosed more chronically than chemotherapies?
they are in theory more toxic to cancer cells, and are therefore better tolerated, and ongoing target blockage may be necessary for benefit
Patients in palliative care may be on these drugs for months or even years
