Print Page Print   EmailEmail   Bookmark Page Bookmark   RSS Feeds RSS

Treatment of Tumors by the Inhibition of Angiogenesis

MCW #1275

 Key Inventor

Richard Roman, PhD

 Background

Recent studies have implicated a potential role for cytochrome P450 metabolites of arachidonic acid in the pathogenesis of several forms of cancer. Cytochrome P450 enzymes of the 4A family (CYP4A) catalyze omega-hydroxylation of arachidonic acid (AA) to form 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE stimulates mitogenic and angiogenic responses both in vitro and in vivo.  These findings suggest that inhibitors of the synthesis or actions of 20-HETE have strong potential as anticancer agents.

 

 

 

 

 Description

Dr. Roman’s lab has investigated the effects of an CYP4A/F inhibitor, HET0016 as well as that of 20-hydroxyeicosa-6(Z), 15(Z)-dienoic acid, (20-HEDE), an inhibitor of 20-HETE responses, on angiogenic responses and on the growth of several human cancer cell lines. HET0016 is very effective at blocking the angiogenic response to VEGF, FGF and EGF in the rat cornea pocket angiogenesis assay. It also inhibits cancer induced angiogenic response associated with the introduction of U251 human glioma cells into the cornea. HET0016 inhibits both basal and growth factor induced (EGF, PDGF, endothelin) proliferation of a variety of cancer cell lines: including  rat 9L gliosarcoma, U251 human glioma, 786-O and 769-P human renal clear cell adenocarcinomas as well as human PC3 prostate cancer and MDA-Mb-231 breast cancer cell lines in vitro. Renal adenocarcinomas synthesize 20-HETE when incubated with arachidonic acid. Both, 20-HEDE and HET0016 reduce proliferation of two different renal adenocarcinomas cell lines in vitro. In an ectopic nude mouse model of clear cell renal carcinomas, chronic treatment with HET0016 or 20-HEDE decreased the growth of these tumors by 80%. This suggests that the antigrowth effects of these chemically dissimilar compounds in these cells is related to inhibition of the synthesis and action of 20-HETE. Chronic treatment of rats with HET0016 (1-10 mg/kg/day) markedly reduced the growth of 9L gliosarcoma tumors (Fig. 1) and improved survival times. This was accompanied by a marked decrease in tumor volume, cell proliferation, and vascularization of the tumors. Overexpression of CYP4A1, a 20-HETE synthase in U251 human glioma cells resulted in a hyperproliferative phenotype in vitro and rapidly growing tumors when the cells were implanted into the brain. These results suggest inhibitors of CYP4A/F enzymes and/or analogs of 20-HETE have potential as anticancer therapeutics. It also suggests that the CYP4 A/F system and 20-HETE contribute to the accelerated growth of a variety of tumors.

 Features

In vivo and in vitro efficacy data for a variety of cancer types including brain, renal, melanoma, prostate, colon, and breast


Large library of compounds available


World-wide patent coverage

 Stage of Development

The technology has been tested in vitro and in vivo. Pharmacokinetic data on these compounds is also available.

 Patents

This technology is covered by numerous US and international patents and patent applications covering composition of matter and methods for modulating angiogenesis and cancer cell proliferation.

Home | About UsFor Inventors | For Industry | FormsTechnologies | Contact Us


 

Office of Technology Development

MEDICAL COLLEGE OF WISCONSIN
8701 Watertown Plank Road
Milwaukee, WI 53226

Summary Information

Mechanism of Action:
Inhibitor
Antagonist

Molecule Type:
Small Molecule

Patent Coverage Type:
Composition of Matter
Method of Use

Geographical Coverage:
Worldwide

Related Areas of Interest:
Cancer

Search

Find Research by

Technology Type

Disease Area

File Types

Contact Us

 

Main Office Phone:   414-955-4362
Main Office Fax:       414-955-6619

 

Joseph Hill, PhD
Vice President
Office of Technology Development
414-955-4381
jhill@mcw.edu

 

Kalpa Vithalani, PhD
Licensing Manager
Office of Technology Development
414-955-4884
kvithalani@mcw.edu

 

James Antczak, PhD
Licensing Manager
Office of Technology Development
414-955-4894
jantczak@mcw.edu