Targeted Chemotherapeutics 2 - Angiogenesis Flashcards
List 6 hallmarks of cancer.
- Sustaining proliferative signalling
- Evading growth suppressors
- Activating invasion and metastasis
- Enabling replicative immortality
- Inducing angiogenesis
- Resisting cell death
Adhesion to the extracellular matric involves..?
Integrins
What is the signature on the cell-surface that is transmitted that normal cells only stick to similar cells?
via cell-adhesion molecules (e.g. cadherins)
Tumour cells secrete proteases like matrix metalloproteinasese (MMPs) and plasmin.. what’s their function?
Degrade extracellular matric facilitating their migration and invasion.
What’s vasculogenesis?
Endothelial progenitor cells (EPCs) arising from various embryonic regions or from adult bone marrow can from vessels in a process referred to as vasculogensis.
What’s angiogenesis?
is a process in which budding from pre-existing vessels gives rise to sprouts of new blood vessels
What’s arteriogenesis?
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
What environmental factor induces HIF-1 expression?
Hypoxia
What effect does hypoxia have on angiogenesis?
Induces HIF-1 expression, upregulates protease expression, leading to basement membrane degradation and pericyte detachment
hat’s the function of PDGF-B ?
Stimulates pericyte attachment and reduces proliferation and VEGF sensitivity
Function of VEGF?
Stimulates DLL4 secretion which binds to Notch-1 receptors: this down regulates VEGFR suppressing proliferation
What do cancer cells rely on for energy?
Glycolysis rather than oxidative phosphorylation for energy
Name the 5 members of the VEGF family.
VEGF-A, VEGF-B, VEGF-C, VEGF-D and placental growth factor (PIGF)
What type of receptors are VEGFR?
Tyrosine kinase receptors
Name some angiogenesis inhibitors.
Bevacizumab, aflibercept, ramucirumab, sunitinib
What type of drug is bevacizumab?
Monoclonal antibody
What type of drug is aflibercept?
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.
What type of drug is ramucirumab?
fully human monoclonal antibody (IgG1) - binds to VEGF-2
What’s sunitinib M.O.A?
Inhibits angiogenesis by diminishing signalling through VEGFR1, VEGFR2, PDGFR and FLT-3
What VEGFR mediates almost all of the known cellular responses to VEGF (growth and permeability)?
VEGFR-2
Where does VEGF-A bind?
VEGFR-1 and VEGFR-2
What do Bevacizumab and Aflibercept inhibit?
Both inhibit VEGF-A thereby inhibiting VEGFR-1 and VEGFR-2
What does Ramucirumab inhibit?
Inhibits VEGFR-2
