Identification of three genetic markers in the ABCB1 gene that can be used to predict the degree of neutropenia and peripheral neuropathy that an individual will experience following paclitaxel treatment

Paclitaxel has been a frontline chemotherapeutic drug used for the treatment of various cancers including metastatic breast cancer and ovarian cancer. Its use has successfully prolonged patient survival. A major drawback of paclitaxel is the cytotoxic side-effects that are associated with it such as myologenic and neurogenic toxicities. The degree of such toxicities varies with individual patients. Predicting the extent of such toxicities following paclitaxel treatment will immensely help in defining optimal treatment schedules for each individual patient. Concurrently, it will significantly improve patient quality of life. This technology describes the identification of three genetic markers in the ABCB1 (MDR-1, P-glycoprotein) gene that can be used to predict the degree of neutropenia and peripheral neuropathy that an individual will experience following paclitaxel treatment. These markers were identified using DNA from blood samples of cancer patients undergoing paclitaxel treatment. This technology can be developed into a routine blood test to identify patient subsets that are more susceptible to paclitaxel treatment associated neutropenia and neuropathy. Applications: (1) Three novel genetic markers that can predict extent of paclitaxel associated toxicities. (2) A screening test based on ABCB1 genotype profiling using patient blood samples that predicts paclitaxel associated neutropenia and peripheral neuropathy. Market: The diagnostic market is worth about $3 billion by 2007 and estimated to grow further. Development Status: (1) The technology is a pilot study currently in the pre-clinical stage of development. (2) A prospective ABCB1 genotype directed clinical trial is foreseen in the near future. Publication: T. M Sissung et al. Association of ABCB1 genotypes with paclitaxel-mediated neutropenia and peripheral neuropathy, To be submitted to Clinical Pharmacology and Therapy.

U.S. Provisional Application No. 60/807,453 filed 14 Jul 2006 (HHS Reference No. E-237-2006/0-US-01) Inventors: William D. Figg (NCI), Alex Sparreboom (NCI), Tristan M. Sissung (NCI), Stephan Mielke (NCI), et al.

Licensees sought: Available for non-exclusive or exclusive licensing. Collaborative Research Opportunity: The NCI Medical Oncology Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize ABCB1 genotyping to predict paclitaxel toxicity. Please contact Betty Tong, Ph.D. at 301-496- 0477, tongb@mail.nih.gov for more information.