Dietary Indole Analogs Inhibit Breast Cancer Cell Invasion
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: Breast cancer recurrence is a potential threat for anyone who has been diagnosed with the disease. Up to half of patients with recurrent breast cancer will eventually have metastatic disease, which is often fatal. Despite considerable effort to improve the survival rates of breast cancer patients, the curability and survival are far from satisfactory. It is important to emphasize that breast cancer only is life threatening when it becomes invasive, at which point it carries the potential for spreading and metastasis. It is invasion that leads to metastasis and turns cancer into an incurable disease. Therefore, preventing cancer invasion is a crucial step in the achievement of cancer cure. 
 
 
 
 
 
 
 
 Cancer recurrence is very likely to result from those undetectable residual cancer cells left after breast cancer surgery. Therefore, if we can develop a safe maintenance therapy to indefinitely suppress any possible residual cancer cells left in patients after primary treatment of breast cancer, we can achieve the equivalent of "cure" of breast cancer. We have identified a novel class of dietary-based indole analogs that appears promising for maintenance therapy after primary treatment of breast cancer to prevent disease invasion and recurrence and therefore increase the overall survival of breast cancer patients. Our dietary indole analogs have proven activities against cancer growth and invasion and have a great likelihood of being safe for long-term disease control. The goal of this proposed STEP award will be to evaluate these promising candidates for maintenance therapy.
 
 
 
 
 
 
 
 Convenience and cost are the most important considerations in the development of long-term maintenance therapeutics. Nevertheless, the treatment must also be safe. Consideration must also be given to patients in older age groups, since they are less likely to tolerate aggressive chemotherapy because of health limitations. Therefore, drugs with well-tolerated or no clinical toxicities and good oral activity suitable for chronic administration will be immensely valuable for breast cancer maintenance therapy. 
 
 
 
 
 
 
 
 In this STEP award we will perform preclinical development of our most promising novel indole analog as a long-term adjuvant therapeutic to prevent cancer recurrence and metastatic spread. We will study our most promising drug candidate for its mechanism of inhibition of cancer metastases, including the cancer cells' survival pathway and their ability to regulate cancer invasion suppressor molecules in cell cultures. Since tumors require a blood supply to survive, grow, and metastasize, inhibition of new blood vessel growth (angiogenesis) has become an exciting target for novel anticancer therapies. Thus, we will also evaluate our analog’s potential for inhibition of angiogenesis.
 
 
 
 
 
 
 
 Animal studies are essential to determine the effectiveness and side effects of the compound as a potential drug for humans. This preclinical study will include evaluation of the efficacy of our most promising analog by tumor histological and pharmacodynamic studies, as well as toxicity studies. Our novel indole analogs are expected to meet all these criteria. They will be orally administered, safe for long-term use, and effective against breast cancer invasion and metastatic spread. Their expected lack of toxic effects will be important for maintaining a patient’s quality of life without debilitation.