AboutMichael Dean Expertise Can answer
General information on the causes of cancer and cancer prevention.
Information on current cancer research and breakthroughs.
The genetics of cancer
The risk of smoking for lung cancer and other cancers, as well as SIDS, heart disease, and vision loss.
Cannot answer
Specific medical questions
Experience Cancer Researcher for over 20 years
Author of the book "Empty Cribs-The impact of smoking on child health" www.artsciencepub.com.
Author of over 200 scientific articles on cancer, genetics and human disease.
Multiple interviews in print, TV and radio media.
Organizations American Association for Cancer Research
American Association of Human Genetics
Publications Scientific journals (Science, Nature, NE Journal Medicine, etc.)
Scientific American, Discovery Medicine, Nature Reviews in Cancer
Education/Credentials PhD. in Biochemistry from Boston University School of Medicine
Awards and Honors Young Investigator award-American Association of Cancer Research
Question Hi, i'm a medical student doing an intercalated degree in pharmacology and I need some help with my dissertation on the anti-cancer drug bevacizumab (avastin)...
I asked another expert for help but he couldn't answer one of my questions - so I was wondering if you help answer...
I understand the basic mechanism of action of the drug. I know it is an antibody that binds to the VEGF recetors 1 and 2, which prevents angiogenesis...
However, angiogenesis does still occur in many cancer cells even when it is treated tumours are treated with avastin...
So my quesiton is -
How does angiogenesis occur in tumours if you block the VEGF receptors 1 and 2 with Avastin - i.e. what other molecular mechanisms do tumours cells have apart from VEGF to stimulate angiogenesis?
Thanks for your help.
Answer Dear Alex,
I am glad to hear of your studies. The answer is rather complicated, and these are early days in Avastin therapy. One problem is that these therapies are used in rather advanced cancers, often in metastatic disease. Not all the cells in the tumor need angiogenesis, so anti-angiogenenic therapy alone will not be a cure.
There are also other antiangiogenic factors as described in this paper:
Relf M et al. (1997) Expression of the angiogenic
factors vascular endothelial cell growth factor, acidic
and basic fibroblast growth factor, tumor growth factor
beta-1, platelet-derived endothelial cell growth factor,
placenta growth factor, and pleiotrophin in human
primary breast cancer and its relation to angiogenesis.
Cancer Res 57: 963–969
Lastly, as with any therapy, tumors can develop resistance. the mechanisms of resistance in Avastin therapy are not well understood, but could involve overexpression or mutation of VEGFR1 or 2.
Here is a bit from a recent review that summarizes some of the challenges:
Nature Clinical Practice Oncology (2007) 4, 181-189
Drug Insight: VEGF as a therapeutic target for breast cancer
Bryan P Schneider and George W Sledge Jr
Numerous challenges nevertheless remain.
Firstly, we do not know which combinations
of VEGF-targeting agents with standard agents
(chemotherapeutic, hormonal, or biologic) will
prove most efficacious. Secondly, we do not
yet have evidence that VEGF-targeting therapy
will prove safe and efficacious in the adjuvant
therapy setting (the one true setting within
which cure is at all a likelihood). Thirdly, the
mechanisms by which cancers become resistant
to antiangiogenic therapies are only now beginning
to be addressed in the laboratory, and are
still largely unexplored in the clinic.66 Finally, we
do not know whether, in the complex calculus of
clinical trials, relatively pure targeting of VEGF
(with agents such as monoclonal antibodies)
will prove equivalent to, superior to, or inferior
to more-promiscuous RTKIs.
