Scholars 2006

2006 Future - Cancer Therapy

Mann-Steinberg Hagit

Tel Aviv University, Sackler School of Medicine, Depatment of Physiology and Pharmacology 

"Inhibition of the Angiogenic Switch of Pancreatic Cancer"

August 2006

Angiogenesis, the formation of capillaries from preexisting blood vessels, is now considered to be a key point for tumor growth. There is a large body of evidence that solid tumors depend on angiogenesis for growth beyond a size of 1-2 mm3. As a result, the microvascular endothelial cell, recruited by the tumor, has become an important second target in cancer therapy. Therefore, one of the most promising treatment approaches today involves the concept of angiogenesis inhibition.

TNP-470 is a synthetic angiogenesis inhibitor that was tested recently as an antiangiogenic/anticancer agent. TNP-470 has shown promise in clinical trials, however, doses necessary for tumor regression, showed signs of neurotoxicity. We recently described the synthesis and characterization of a novel non-toxic, water-soluble N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-TNP-470 conjugate, named caplostatin. Conjugation of TNP-470 to HPMA copolymer prolonged the circulating lifetime of the drug and increased its accumulation in angiogenic tissue such as the tumor vascular bed. Furthermore, caplostatin was unable to cross the blood brain barrier (BBB), eliminating its neurotoxicity.

In order to improve the therapeutic index of caplostatin even further we propose to add to this conjugate a targeting moiety such as RGD that will actively target it to the proliferating endothelial cells in the tumor surrounding. We plan to test this novel conjugate and its ability to inhibit angiogenesis on several mouse models and to elucidate its mechanism of action. 

Update November 2010: 
It has been 4-5 years since I was awarded the Dan David Prize and I still remember it as a great honor and I know I owe it the chance to start my postdoctoral position with the right foot.

During this time that had passed I have continued my postdoctoral research at the Tel-Aviv University at Dr. Ronit Satchi-Fainaro's lab, published a few scientific papers and was the recipient of the Israel Cancer Research Fund Postdoctoral Fellowship. 

After completeing my postoctoral position, I have left the academic world and moved to the biotechnology industry where I am also doing very well.