Targeted cancer therapies Flashcards
Cancer definition
A disease of populations of cells that live, divide, invade and spread without regards for normal limits
What are the 6 key common phenotypic characteristics of cancer cells?
Evade apoptosis Sustained angiogenesis self sufficiency in growth signals Insensitivity to anti growth signals tissue invasion and metastases limitless replicative potential
Chemo targets and examples using cell cycle
Target dividing cells (hence the ST, more occurring in cancer) so blood cytopenias an hair loss common
Methotrexate- S phase, DNA synthesis inhibitor
Paclitaxel- acts on spindle, M phase specific
What are three kinds of targeted cancer therapy aimed at oncoproteins?
Small molecular drugs that block enzymes e.g. gefitinib, imatinib
Monoclonal antibodies that bind to growth factors, trastuzumab, bevacizumab
Discuss example of chronic myeloid leukaemia?
Abnormal fusion protein?
Drug used? (also used for GI stromal tumours)
Has a characteristic chromosome translocation, Philadelphia chromosome (9;22). (22)
Accumulation of myeloid leukaemia cells in marrow and blood
Abnormal fusion protein bcr-abl, causing self sufficiency of growth
Imatinib used, is a tyrosine kinase inhibitor of brc-abl, that binds to ATP binding site, stopping activity.
Immune checkpoint modulation
Monoclonal antibodies that bind to things that allow T cells to attack tumours.
IImmune related side effects however like colitis, dermatitis
What does gefitinib do?
Is a EGFR tyrosine kinase inhibitor.
Side effects are rash and diarrhoea (due to EGFR receptors here)
What can be said about genetically acquired resistance?
A mutation, in the example of gefitinib, caused its ineffectiveness
Individualisation of therapy
Can be done by genetic testing, to detect somatic mutations to direct patients to targeted therapies
