8. targeted therapy in cancer

Question 1

what do targeted therapy in cancer do?

Answer 1

Exploits biological weaknesses in tumours

• Faulty genes
• Faulty signalling systems
• Tumour growth
• Angiogenesis

Question 2

Tamoxifen

Answer 2

Hormone based therapy

• Blocks oestrogen as a selective estrogen-receptor modulator (SERM)
• Prevents breast cancer- stops spread
• Reduces growth of oestrogen-driven breast cancer
• Used in estrogen receptor positive (ER+) breast cancer
• As a receptor modulator: prevents bone loss via oestrogenic effects
• Early menopause as blocking effect of oestrogen

Question 3

which hormone promotes growth in metastatic cells

Answer 3

oestrogen

Question 4

Aromatase inhibitors

Answer 4

• Prevents peripheral conversion of androgen to oestrogen
• second approach following tamoxifen

Question 5

HER2 receptor

Answer 5

• Naturally present in low levels
• But over expressed in some cancers eg breast cancer
  
  • More likely in older patients
• Due to oncogene (ERBB2)
• Affects gene transcription and cell cycle
  *

Question 6

Trastuzumab

Answer 6

• Monoclonal antibody- specific
• Targets human epidermal growth factor receptor-2 (HER2)
• Early breast cancer and metastatic breast cancer with HER2 positive tumours
• prevents production of VEGF

Question 7

Epidermal Growth Factor Receptor (eGFR)

Answer 7

• ‘Small molecule’ approach
• Certain Lung and pancreatic cancers
• Inhibits tyrosine kinase to target over proliferation of receptor

Question 8

Tyrosine kinase activity which chromosome can cause activity

Answer 8

• Philadelphia Chromosome associated with Chronic Myeloid Leukaemia
• Ph chromosome produces bcr-abl protein which has tyrosine kinase activity.
• Tyrosine kinase leads to uncontrolled cell proliferation
• Imatinib inhibits TK activity
• Selective inhibitor very effective for Chronic Myeloid Leukaemia
• Trials - >90% pts with CML alive after 5 years
• Gastro-intestinal stroma tumours

Question 9

Proteasome inhibitor

Answer 9

• Proteasomes: cellular structures which degrade proteins- including those that have pro-apoptotic factors
• Inhibition of intracellular proteasomes alters the regulation of intracellular proteins

Question 10

Anti-VEGF

Answer 10

also targeted