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antiangiogenic drugs as a targeted drug therapy

ambitious team EPSF
by

asmaa ali

on 14 April 2016

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Transcript of antiangiogenic drugs as a targeted drug therapy

Content
Angiogenesis
Angiogenesis and cancer
Antiangiogenic drugs
Approved uses
side effects and resistance
conclusion
what is Angiogenesis?
A new blood vessel is coming to be created
Angiogenesis and Cancer
DID we make it ?
Yes we did.
Wounds that don't heal
sever bleeding
hypertension
infusion reaction
so,we can target cancer cell from this point
Antiangiogenic Drugs as a Targeted Drug Therapy
to be more specific: :
Creating new blood vessel is done by two mechanisms:
(a)Vasculogenesis:
de novo synthesis of blood vessels
(b) Angiogenesis:
creation of new vessels from already existing vessels.

when do we need it?
during embryogenesis
female reproductive system
pathological conditions:
(wound healing and tumor growth)
VEGF + PDGF
a tumor needs an independent blood supply, which is acquired by the expression of growth factors that recruit new vasculature from existing blood vessels
tumor growth and metastasis is angiogenesis-dependent
excessive production of angiogenic growth factors
excessive expression of their receptors
VEGF
PDGF
Tyrosine kinase receptor
Antiangiogenic drugs
The goal of their use:
a) therapeutic goal
tumor shrinkage
inhibit metastasis
synergistic effect with other drugs
b) protective goal
decrease systemic side effects
improve patients' quality of life
classification of antiangiogenic drugs
1-vascular endothelial growth factor receptor (VEGFR) inhibitors:
a) Tyrosine kinase and multi-kinase inhibitors:
b) Monoclonal antibodies
2-inhibitors of endothelial cell proliferation.

Bevacizumab (Avastin®):
monoclonal antibody against VEGF
FDA Approved for:
1st angiogenesis inhibitor that was
slow tumor growth
extend the lives of patients.

Recurrent glioblastoma - alone
NSCLC - with carboplatin and paclitaxel
Metastatic Kidney cancer - with interferon alfa
Advanced Cervical cancer - with paclitaxel and cisplatin
Sorafenib (Nexavar®)
small molecular inhibitor of several tyrosine protein kinases including:
VEGFR
PDGFR
Raf, MEK, ERK
Approved for:
advanced kidney cancer
advanced liver cancer
I-resistant thyroid cancer
and most important:
TKIs against the ABL family:
Imatinib
(gleevec®)
Nilotinib
(Tasigna®)
and much more

Did our bodies accept these drugs?
Take care if you are:
undergoing surgery
pregnant
breast feeding mother
How did cancer deal with these drugs?
response
acquired resistance
Future Look
there is a must to develop a new class of drugs that inhibit the mutant VEGF and its receptor, and not the normal wild types, and to target the escaping mechanisms of the cancer.
Ambitious Team
EPSF-Helwan

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