The Cancer Prevention Research Institute of Texas (CPRIT) has awarded two scientists from the Cancer Therapy & Research Center (CTRC) in San Antonio with $3.99 million in new grants to support the development of next-generation medication to treat breast cancer. CTRC researcher Rong Li, Ph.D., is working on a project to improve existing drugs’ precision and effectiveness, while Ratna Vadlamudi, Ph.D., is developing an innovative compound that is able to reduce tumor drug resistance.
Dr Li, a professor of molecular medicine at CTRC, is the principal investigator in a research project that that will analyze the potential of an existing drug used for treating hot flashes as an anti-tumor therapy, and design other agents that he and the research team believe will enable the drug to be more precise. “It balances feasibility and innovation,” Li explained in a recent press release.
Specifically, Li will focus on two receptors that drive estrogen activity, Estrogen Receptor (ER) alpha and Estrogen Receptor beta. While much is already known about the former, he believes in the potential of the latter, calling it the “Cinderella sister.” “It has a lot of similar characteristics, but in many cases it behaves in the opposite manner,” Li said. “And in many cases, unlike ER alpha, it inhibits tumor growth.”
Since ER beta is detected in about half of all breast cancers, the investigator and his team will seek to tap into its tumor-suppressing potential. To do this, the research team will analyze a drug currently in development by pharmaceutical company Ausio for the treatment of menopause symptoms. In addition to revealing the safety of the drug, Ausio’s clinical trials revealed that their therapy turns the ER beta switch on. As a result, Li’s team established an agreement with the company and will be testing the drug in combination with other agents being developed at the CTRC.
“The novel part of this work is that we’ve discovered how to turn on the ER beta function, and also how to inhibit the process that turns it off. This proposal seeks synergy among these three approaches that might maximize the anti-tumor activity of ER beta,” added Li.
Tackling Tumor Resistance To Drugs
Dr. Vadlamudi, who is a professor of obstetrics and gynecology at CTRC, is leading a CPRIT-funded project that will test a drug that is able to prevent the development of tumor drug resistance in patients suffering from breast cancer. “This funding will help us develop these first-in-class cancer therapy drugs that address the critical need of targeting therapy resistance and metastasis of breast cancer,” said Vadlamudi.
Vadlamudi’s research focuses on studying the mechanisms of treatment-resistant cells, since many patients develop resistance to medication after an initial response. Typically breast cancer drugs are antiestrogens or aromatase inhibitors that are used to target breast tumors, which grow in response to the estrogen hormone. However, due to drug resistance, the tumors tend to mutate an estrogen receptor (ESR1) and continue to develop through ESR1-driven pathways.
To combat this, the research team created a ESR1 coregulator binding inhibitor (ECBI), which is a small-molecule drug that is expected to block the multiple oncogenic pathways resulting from resistant cells and avoid drug resistance. In addition, the researchers also expect that the ECBI produces fewer side effects and is able to delay chemotherapy treatments.
“Huzzah!” said the director of the CTRC, Ian M. Thompson Jr., M.D. “This is a tangible confirmation of the exceptional merit of the science and clinical care provided by our CTRC scientists and physicians.” The grants provided by CPRIT, which are both early translational research awards, will enable the researchers to advance their projects in the laboratory in order to start clinical trials.
In addition to the two CTRC scientists, investigators from the University of Texas at San Antonio are also collaborating on the projects through the Center for Innovation in Drug Discovery, which is shared by the two institutions, as well as from UT Southwestern Medical Center and University of Texas at Dallas.
CPRIT continues to support the fight against cancer as well as finding a cure for the disease, with breast cancer being one of the organization’s main priorities. Last month, CPRIT awarded $1.5 million to the University of Texas Southwestern Medical Center to support the expansion of genetic screening directed for rural and underserved areas. The main purpose of the project is to spearhead the expansion from the current 6 counties to a total of 22 in North Texas.