University of Arkansas for Medical Sciences
Little Rock, AR
The American Thyroid Association has awarded a 2018 Research Grant to Brendan Frett, PhD, Assistant Professor in the College of Pharmacy at the University of Arkansas for Medical Sciences. The title of Dr. Frett’s project is “Dual Inhibition of RET and Aurora B to Study the Simultaneous Regulation of Multiple Oncogene Pathways in Medullary Thyroid Cancer.”
Since its inception in 1971, the War on Cancer has resulted in significant treatment breakthroughs. One of the most important was the discovery of cancer-promoting oncogenes (genes with the potential to cause cancer). Researchers theorized that oncogenes could be strategically targeted while sparing normal cells, which sparked the era of precision medicine for oncology. Early medicine discoveries were quickly followed by the realization that secondary mutations in cancers often resulted in resistance to the drugs and relapse of the disease. This was solved by generating inhibitors that achieved activity on multiple forms of the oncogenes. However, additional cancer-promoting pathways were activated by the oncogenes. Therefore, although precision medicine for oncology has had great upfront success, the onset and degree of resistance lowers the effectiveness of many treatments. How is it possible to avoid this resistance?
The majority of thyroid cancers (TC) are curable through surgery, radiation, and chemotherapy, with a five-year survival rate of 98%. However, TC can present in certain forms that are highly aggressive, such as metastatic medullary thyroid cancer (MTC). Researchers have identified drivers specific to MTC (RET and VEGFR2, among others) through comprehensive investigation, which led to the clinical development of precision-medicine therapies that target those oncogenes. However, through RET-oncogene mutations and other cancer-promoting pathways, MTC tumors can develop resistance to precision medicine, in which case treatment benefit becomes limited.
The ultimate goal for this project is to uncover pioneering precision-medicine strategies and innovative biology and treatment paradigms that can be used to more effectively combat resistant thyroid disease. More specifically, Dr. Frett’s laboratory plans to develop a dual-targeted compound that acts on both RET and cell cycle oncogenes, employing single-agent polypharmacology (SAP) and synergistic medicinal chemistry (SMC). They will focus on understanding MTC-resistance mechanisms. As medicinal chemists, they specialize in the design and development of unique tools to help analyze MTC biology. For this project, they want to investigate the use of precision medicine to target multiple, unrelated cancer-promoting pathways.
- First, they will design tractable inhibitors to block the RET oncogene, because MTC is heavily promoted by the RET oncogene.
- Second, they will expand the RET inhibitor to block the ability of MTC cells to divide, since uncontrolled cell growth is a hallmark of cancer.
- They will repeat the two-step process with cell cycle oncogenes.
Dr. Frett expects that this method of targeting MTC will significantly help delay the degree and onset of resistance to precision medicine.
In 2014, Dr. Brendan Frett received his PhD in Pharmaceutical Sciences, with an emphasis in Drug Discovery and Development, from the University of Arizona. He also received postdoctoral training in Medicinal Chemistry and in Pharmaceutics at the University of Arizona. He has successfully transferred academic-based discoveries to pharmaceutical companies for clinical development, specializing in the development of therapies for orphan diseases (those that offer little financial incentive for the private sector to develop and sell new medications that would treat or prevent them, either because the diseases are rare or because they are not common in the “developed” world). Dr. Frett is interested in pursuing translational research projects, where research completed in his laboratory can directly help patients. Specifically, he investigates resistance mechanisms and the design of next-generation precision-medicine therapies for thyroid cancer. He is interested in tailoring precision medicine to the unique pathology of MTC to generate “synergistic” medicine.
Dr. Antonio Di Cristofano, Chair, ATA Research Committee, says, “The ATA research grant program represents a unique and invaluable mechanism to foster the development of a new generation of basic, translational, and clinical researchers. Through this program, we allow these outstanding young scientists to test innovative hypotheses and generate preliminary data that will give them a significant competitive advantage when applying for traditional NIH-type funding.
This year we received 63 applications from 18 countries, spanning the whole spectrum of thyroid-related research. While, through a rigorous process, we have selected the most promising projects for funding, at the same time we regret we had to leave behind a number of excellent proposals. We are extremely thankful for the support we receive from members and organizations, including thyroid cancer survivors, which makes this outstanding program possible and allows the ATA to nurture the next generation of leaders in thyroidology.”
The American Thyroid Association (ATA) has awarded 99 thyroid research grants totaling over $2.8 million since the inception of the Research Fund. In addition, the ATA rigorously manages the selection of research projects and the distribution of over $1.8 million generously donated to the ATA specifically for research grants from: ThyCa, the Thyroid Cancer Survivors’ Association, Inc.; Bite Me Cancer; and the Thyroid Head and Neck Cancer Foundation.
The Thyroid Cancer Survivors’ Association, Inc. (ThyCa), has provided funding since 2003 in support of 72.5 special research grants totaling $2,084,375 focused on thyroid cancer and medullary thyroid cancer. In 2018 ThyCa is supporting half of a new medullary thyroid cancer grant with Bite Me Cancer, two new thyroid cancer research grants, and four renewing grants. ThyCa is a member of the ATA Alliance for Patient Education. Find out more at www.thyca.org.
Bite Me Cancer (BMC) is our newest grant funder, supporting 8.5 thyroid cancer grants since 2014 for a total of $201,250. BMC will be supporting a half of a new medullary thyroid cancer grant in 2018 with ThyCa and one renewing thyroid cancer grant. BMC is a member of the ATA Alliance for Patient Education. Find out more at www.bitemecancer.org.
The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis, and treatment of thyroid disorders and thyroid cancer. ATA is an international, individual membership organization for over 1,700 clinicians and researchers from 43 countries around the world, representing a broad diversity of medical disciplines. It also serves the public, patients, and their families through education and awareness efforts.
Celebrating its 95th anniversary, ATA delivers its mission through several key endeavors: the publication of highly regarded monthly journals, Thyroid®, Clinical Thyroidology®, VideoEndocrinology, and Clinical Thyroidology for the Public; annual scientific meetings; biennial clinical and research symposia; research grant programs for young investigators; support of online professional, public, and patient educational programs; and the development of guidelines for clinical management of thyroid disease.
Find out more about ATA at www.thyroid.org.