Targeted Chemotherapeutics 2 - Angiogenesis

Question 1

List 6 hallmarks of cancer.

Answer 1

1. Sustaining proliferative signalling
2. Evading growth suppressors
3. Activating invasion and metastasis
4. Enabling replicative immortality
5. Inducing angiogenesis
6. Resisting cell death

Question 2

Adhesion to the extracellular matric involves..?

Answer 2

Integrins

Question 3

What is the signature on the cell-surface that is transmitted that normal cells only stick to similar cells?

Answer 3

via cell-adhesion molecules (e.g. cadherins)

Question 4

Tumour cells secrete proteases like matrix metalloproteinasese (MMPs) and plasmin.. what’s their function?

Answer 4

Degrade extracellular matric facilitating their migration and invasion.

Question 5

What’s vasculogenesis?

Answer 5

Endothelial progenitor cells (EPCs) arising from various embryonic regions or from adult bone marrow can from vessels in a process referred to as vasculogensis.

Question 6

What’s angiogenesis?

Answer 6

is a process in which budding from pre-existing vessels gives rise to sprouts of new blood vessels

Question 7

What’s arteriogenesis?

Answer 7

refers to the stabilisation of these new sprouts by pericytes and smooth muscle cells (SMCs). Arteriogenesis is critical for the new vasculature to become stable, mature and functional

Question 8

What environmental factor induces HIF-1 expression?

Answer 8

Hypoxia

Question 9

What effect does hypoxia have on angiogenesis?

Answer 9

Induces HIF-1 expression, upregulates protease expression, leading to basement membrane degradation and pericyte detachment

Question 10

hat’s the function of PDGF-B ?

Answer 10

Stimulates pericyte attachment and reduces proliferation and VEGF sensitivity

Question 11

Function of VEGF?

Answer 11

Stimulates DLL4 secretion which binds to Notch-1 receptors: this down regulates VEGFR suppressing proliferation

Question 12

What do cancer cells rely on for energy?

Answer 12

Glycolysis rather than oxidative phosphorylation for energy

Question 13

Name the 5 members of the VEGF family.

Answer 13

VEGF-A, VEGF-B, VEGF-C, VEGF-D and placental growth factor (PIGF)

Question 14

What type of receptors are VEGFR?

Answer 14

Tyrosine kinase receptors

Question 15

Name some angiogenesis inhibitors.

Answer 15

Bevacizumab, aflibercept, ramucirumab, sunitinib

Question 16

What type of drug is bevacizumab?

Answer 16

Monoclonal antibody

Question 17

What type of drug is aflibercept?

Answer 17

Recombinant fusion protein consisting of vascular endothelial growth factor (VEGF)- binding portions from the extracellular domains of human VEGF receptors 1 and 2, that are fused to the Fc portion of the human IgG1 immunoglobulin.

Question 18

What type of drug is ramucirumab?

Answer 18

fully human monoclonal antibody (IgG1) - binds to VEGF-2

Question 19

What’s sunitinib M.O.A?

Answer 19

Inhibits angiogenesis by diminishing signalling through VEGFR1, VEGFR2, PDGFR and FLT-3

Question 20

What VEGFR mediates almost all of the known cellular responses to VEGF (growth and permeability)?

Answer 20

VEGFR-2

Question 21

Where does VEGF-A bind?

Answer 21

VEGFR-1 and VEGFR-2

Question 22

What do Bevacizumab and Aflibercept inhibit?

Answer 22

Both inhibit VEGF-A thereby inhibiting VEGFR-1 and VEGFR-2

Question 23

What does Ramucirumab inhibit?

Answer 23

Inhibits VEGFR-2