"Normalizing tumor vasculature to treat cancer: From mathematical model to

mouse to man"

Rakesh K. Jain, Ph.D.

Andrew Werk Cook Professor of Tumor Biology
Harvard Medical School
Director, Edwin L. Steele Laboratory for Tumor Biology
Department of Radiation Oncology
Massachusetts General Hospital
100 Blossom St, Cox 7
Boston, MA 02114
Tel: (617) 726-4083
Fax: (617) 724-1819
E-mail: jain@steele.mgh.harvard.edu
url: http://steele.mgh.harvard.edu

Cancerous tumors require blood vessels to grow and spread to other organs.
Dr. Jain demonstrated that the blood vessels of tumors are abnormal – not
only in their structure, but also in their function. Using a mathematical
model, he showed consequences of this abnormality – specifically, how this
abnormality contributes directly to malignant properties of a cancer as well
as prevents treatments from reaching and attacking tumor cells. Dr. Jain
proposed a novel concept that “normalizing” tumor vessels would allow
cancer therapies to penetrate the mass and to function more effectively. He
then went on to show first in mice and then in cancer patients that drugs
originally deigned to destroy tumor vessels could, paradoxically, also repair
them, creating a window of opportunity to attack the cancer most effectively.
This concept is also opening doors to treating other vascular diseases, such
as age-related wet macular degeneration, a leading cause of blindness, and
neurofibromatosis-2, which can lead to deafness.

References:

1. R. K. Jain, Normalizing tumor vasculature with anti-angiogenic therapy: a new

paradigm for combination therapy. Nature Medicine, 7:987-989 (2001).
2. R. K. Jain, Normalization of the tumor vasculature: An emerging concept in
anti-angiogenic therapy of cancer. Science, 307: 58-62 (2005).
3. R. K. Jain et al, Lessons from phase III trials of anti-VEGF therapy for cancer.
Nature Clinical Practice Oncology, 3: 24-40 (2006).
4. R. K. Jain, R. Tong and L. L. Munn, Effects of vascular normalization
on interstitial hypertension, peri-tumor edema and lymphatic
metastasis: Insights from a mathematical model. Cancer Research 67:
2729-2735 (2007).
5. R. K. Jain, Taming vessels to treat cancer. Scientific American,
298:56-63 (2008).
6. R. K. Jain, Lessons from multidisciplinary translational trials on
antiangiogenic therapy of cancer. Nature Reviews Cancer, 8:309-316
(2008).
7. R. K. Jain et al. Biomarkers of benefit and resistance to antiangiogenic
therapy. Nature Reviews Clinical Oncology 6: 327-338 (2009).
8. R. K. Jain. A new target for tumor therapy,” New England Journal of
Medicine 360: 2669-71 (2009).
9. S. Plotkin et al. Hearing improvement after bevacizumab in patients
with neurofibromatosis 2. New England Journal of Medicine 361: 358-
369 (2009).
10. P. Carmeliet and R. K. Jain, Nature (in press).