Tumor Angiogenesis

Question 1

How is Angiogenesis induced when cancer grow

Answer 1

When cells get out of reach of oxygen, as for cancer bulks, HIF-1a transcribe VEGF. VEGF is secreted by the cancer cells and create a gradient

VEGF cause normal epithelial cells to differentiate into Tip cells consisting of filopodia. Filopodia have VEGF-r on them and when they are activated they start to migrate towards the source of VEGF. By elongation of the tube and proliferation of the stalk cells behind it –> creating new blood vessels

Also collagen promote the formation of blood vessels

Question 2

What does the Anti-angiogenic drug target

Answer 2

Inhibition of collagen –> Endostatin

Inhibition of plasminogen –> Angiostatin, anti-blood clotting drug

VEGF-Ab “Avastin” –> binds to VEGFR2 tyrosine kinase transmembrane receoptor for VEGF

Inhibition of the intracellular cascade - novartis

Question 3

theories; why won’t anti-angiogenic work

Answer 3

• Vessels in tumors are messier and actually get more normal when treated, increasing blood flow
• The new vessels are protected by pericytes around them, producing molecules that interfere with anti-angiogenic treatment
• When blocking VEGF, tumors might start producing other factors that bypass this inhibition and they regain their angiogenic abilities