One of the major hindrances to successful cancer chemotherapy is multi-drug resistance (MDR), which is frequently caused by the increased expression or activity of ABC transporter proteins.  Research has generally been directed to overcoming MDR during cancer therapy by inhibiting the activity of ABC transporters.  However, compounds that inhibit ABC transporter activity often elicit strong and undesirable side-effects, restricting their usefulness in therapy.

In an alternative approach to reducing the debilitating effects of MDR in cancer therapy, scientists at the National Cancer Institute identified a family of compounds whose antiproliferative effects were actually enhanced in cells with MDR.  These compounds included NSC 73306, a specific compound that increased the chemosensitivity of cells that overexpress ABC transporters without inhibiting ABC transporter activity.  This invention concerns new analogs of NSC 73306 with improved selectivity and solubility, and the use of the analogs as therapeutics.

Applications: 

•    Treatment of cancers associated with multi-drug resistance, either alone or in combination with other therapeutics

•    Development of a pharmacophore for improved effectiveness in treating cancers associated with multi-drug resistance

Advantages:

•    The agents capitalize on one of the most common drawbacks to cancer therapies (MDR) by using it as an advantage to treating cancer

•    Increased specificity allows these analogs to be tailored to treating cancers associated with the overexpression and hyperactivity of particular ABC transporters

•    Increased solubility allows greater access of the agent to tumor cells, increasing therapeutic effectiveness of the agents

Benefits:

Cancer is the second leading cause of death in United States and it is estimated that there will be approximately 600,000 deaths caused by cancer in 2007.  Improving the quality of life and duration of life of cancer patients will depend on chemotherapies with increased effectiveness and reduced toxicity, thus this technology can contribute significantly to a social cause.  Furthermore, small molecule cancer therapy technologies have a potential market of more than $2 billion. 

U.S. Provisional Application No. 61/027,712 filed 11 Feb 2008 (HHS Reference No. E-017-2008/0-US-01)

Inventors:

Matthew D. Hall et al. (NCI)

Licensees Sought. 

Collaborative Research Opportunity:

The National Cancer Institute’s Laboratory of Cell Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize for the clinic, compounds that demonstrate MDR1-inverse activity.  Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.