18 - Targeted Cancer therapies

Question 1

What is cancer

Answer 1

A disease of populations of cells that live, divide, invade and spread without regard to normal limits
Normally cell growth, death and location are tightly regulated in the body

Can be caused by exogenous carcinogens, DNA replicaiton errors, or inherited

-oncogenes activated and tumour supressor genes inactivated

Question 2

Chemotherapy targeting cycling cells

Answer 2

• targets cycling cells without discriminating between normal or cancer cells
• Selective toxicity achieved due to higher numbers of cycling cells present in tumour than normal tissue
• Adverse effects of chemotherapy are due to inhibition of proliferation of normal cells

Question 3

Targeted cancer therapy

Answer 3

• Drug treatments that inhibit oncoproteins that drive tumour development and progression
• effective and safer than chemotherapy - allows individualization of therapy based on genetic testing
• smaller molecular drugs - block specific enzymes or growth factor receptors )e.g imatinib or gefitinib)
• Monoclonal antibodies - bind to growth factors or their receptors

Question 4

Chronic myleoid leukaemia

Answer 4

chromosomal translocation in the philadephia chromosome (22 and 9)

• encodes for a protein with tyrosine kinase activity and stimulates growth to drive chronic myloid leukemia
• treatment - previously chemotherapy and immunotherapy and now - targeted therapy
• imatinib - fusion protein with tyrosine kinase activity to suppress driver of CML
• imatinib acts by inhibiting binding site for ATP and blocks the phosphorylation of tyrosine residues on the substrate preotin so this means ti cannot work - stops the transduction pathways that induce leukemai

Question 5

Immune checkpoint modulation

Answer 5

Monoclonal antibodies bindign cytotoxic T lymphocyte antige t4 - e.g ipilimumab - wuill suppress t cell immune cytotoxicity and enable tumour cells to be attacked by t cells
-melanoma, non-small cell lung cancer
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Question 6

Example of person with Adenocarcinoma but with EGFR mutation

Answer 6

Gefitinib - which is an EGFR tyrosine kinase inhibitor

• however some people have a mutation of this and so the affinity for binding to the protein is reduced and less effective drug treatment
• can use genetic testing to test for these mutations