Angiogenesis Inhibitors

Question 1

Why inhibit angiogenesis?

Answer 1

Required for tumour growth and critical for metastasis

Question 2

Important pro-angiogenic factors?

Answer 2

Targets for inhibition of angiogenesis

HYPOXIA INDUCIBLE FACTOR –>

All tyrosine kinases

• Vascular endothelial growth factor
• Basic fibroblast growth factor
• Platelet derived growth factor
• Transforming growth factor alpha

Question 3

VEGF and VEGF receptor inhibitors

Answer 3

Bevacizumab = VEGF inhibitor

Sunitinib and Sorafenib = VEGF-receptor and PDGF-receptor inhibitors

Question 4

Sunitinib and Sorafenib

Answer 4

VEGF-R and PDGF-R inhibitor

Sunitinib = Renal cell cancer
Sorafenib = RCC and HCC

Multikinase inhibitors –> redcues tumour proliferation and angiogenesis

Side effects:

• Hypertension - PREDICTOR OF DISEASE RESPONSE
• Reversible posterior leukoencephalopathy
• Renal dysfunction
• Haemorrhage

Question 5

mTOR inhibitor

Answer 5

Inhibits hypoxia inducible factor

Temsirolimus

Renal cell cancer

Side effects:

• Oral ulceration
• Rash
• Fatigue
• Hypertension
• Hand and foot syndrome
• Diarrhoea
• Infections
• PNEUMONITIS

Question 6

EGFR Inhibitors

Answer 6

Block signalling of transforming growth factor alpha
–> reduces tumour cell proliferation and survival and decreases mets

NSCLC, Prostate, Gastric, breast, colorectal, pancreatic and ovarian cancer

Erlotinib, Gefitinib, cetuximab, panitumumab

ACNEIFORM RASH = predicts treatment response