Novel Agents for Treatment of Advanced Breast Cancer
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: In spite of major advances in early detection and adjuvant therapy, advanced breast cancer remains a major clinical and human problem. There is an urgent need for new therapies and novel agents that are more effective than those currently available for the treatment of advanced breast cancer and will improve the survival rates, extend survival time, and improve quality of life for survivors. In our existing California Breast Cancer Research Program project, we discovered a novel class of compounds that is based on a substance found in certain vegetables and looks very promising as a effective and safe agent to halt breast cancer before it becomes incurable. Our proposed project addresses the BCRP priority issue of Innovative Treatment Modalities and has as its goal preclinical development studies to further evaluate our best compounds and prepare for future clinical trials.
 
 
 
 
 
 
 
 Although breast tumors can be classified as hormone-dependent or hormone-independent according to their hormone receptor status, most hormone receptor-positive breast tumors actually consist of mixtures of hormone-dependent and hormone-independent cells, and the hormone-independent tumor cells are not destroyed by hormonal therapy. Clinical experience reveals that the initial benefits of antiestrogen treatment in breast cancer tend to decrease with time as hormone-independent cancer cells predominate, and monitoring appears to show that estrogen-dependent tumors eventually become estrogen-independent. Therefore, curative drug therapy of cancer must control both hormone-dependent and -independent tumor cells in heterogeneous breast tumors to maximize cancer cell inhibition and give the best chance of complete remission. Other important qualities for new breast cancer therapeutics are good oral bioavailability and minimal toxicity and side effects.
 
 
 
 
 
 
 
 We have discovered a novel class of compounds, analogs of naturally occurring tumor inhibitors that exhibit excellent growth inhibitory activity against both estrogen-responsive and estrogen-nonresponsive human breast cancer cells. They also possess high potency against tamoxifen-resistant human breast cancer cells and display no undesired estrogenic side effects. Since these compounds are analogs of indoles found in some vegetables, they are likely to be safe for long-term administration. This research project will focus on preclinical development of our three most promising compounds by studies in animals to evaluate their antitumor activity, oral bioavailability, and possible toxicological effects and laboratory studies to identify their mechanism of action.
 
 
 
 
 
 
 
 Successful development of our novel drugs for clinical use will have a significant impact on reducing the human and economic costs of breast cancer because they will be orally administered, safe for long-term use, and effective against estrogen-dependent, and estrogen-independent, and tamoxifen-resistant breast cancer. Their expected lack of toxic effects will be an important benefit because patients will not be debilitated by the treatment. No existing therapeutic drug for advanced breast cancer has all these desirable qualities.