More than $3 million granted to Karmanos researcher’s lab to combat therapy-resistant cancers
A Karmanos Cancer Institute and Wayne State University (WSU) scientist has secured $3,032,353 to fund a study that could introduce a new class of drugs tailored for patients with therapy-resistant cancers.
Hyeong-Reh Kim, Ph.D., member of the Tumor Biology and Microenvironment Research Program (TBM) at Karmanos, is the principal investigator on the project “A novel AR degrader in castrate-resistant prostate cancer.” Her lab at the WSU School of Medicine was awarded the money from the National Cancer Institute.
The goal is to develop a new class of drugs that effectively degrade both wild-type androgen receptor (AR) proteins and AR variants in prostate cancer. The Kim laboratory has been working to uncover the molecular and cellular mechanisms underlying human cancer progression and metastasis, identify therapeutic targets, and develop novel therapeutics for patients with therapy-resistant cancers, including advanced head and neck cancers and castrate-resistant metastatic prostate cancer.
The receptors for androgens, the group of male sex hormones, play a critical role in all stages of prostate cancer. While many prostate cancer patients initially respond to hormone therapies, significant numbers of patients develop castrate-resistant prostate cancer.
Clinical studies have shown that castrate-resistant prostate cancer often involves androgen receptor variants that lack the ligand binding domain, making this hormone receptor constitutively active and resistant to hormone therapy.
“The innovations in our study include the development of a new therapeutic platform using autophagy-targeting chimera (AUTOTAC) for oncoprotein degradation,” said Dr. Kim, who is also a professor of Pathology at WSU School of Medicine. “This novel therapeutic platform is composed of a target-binding small molecule linked to an autophagy ligand. The AUTOTAC brings the targeted oncoprotein to the protein degradation machinery, involving autophagosome and lysosome, leading to the efficient removal of oncoproteins.
“Using a natural ligand or a synthetic small molecule that binds the protein of interest, the AUTOTAC can be utilized for the removal of unwanted proteins. Our study will help establish the foundation for a revolutionary drug development platform in a wide array of human diseases,” Dr. Kim added.
In collaboration with Harold Kim, M.D., radiation oncologist, member of the Gynecologic Oncology, Head and Neck Oncology, Multiple Myeloma and Amyloidosis, Neuro-Oncology and Thoracic Oncology Multidisciplinary Teams (MDTs), member of the Molecular Imaging Research Program at Karmanos, and professor at WSU; and Joseph Rakowski, Ph.D., associate professor; and the new Barber Integrative Metabolic Research Team, the Kim laboratory is engaged in the development of radiosensitizers utilizing the AUTOTAC platform or inducers of lipolysis.
“This is a truly collaborative project involving many co-investigators, including Dr. Yong Tae Kwon at Seoul National University and Drs. Elisabeth Heath [leader of the Genitourinary Oncology MDT, member of the Phase 1 Clinical Trials MDT and TBM], Seongho Kim [Molecular Therapeutics Research Program – MT], Dongping Shi [Pathology – WSU], Michael Cher [member of the Genitourinary Oncology MDT and TBM], Lisa Polin [member of MT] and Sijana Dzinic [member of MT] at the Wayne State University School of Medicine. In my laboratory, Drs. Abdo Najy and Tri Pham, Alaleh Zamiri, M.D. – a Ph.D. student – and Jenna Poole will work on this project. We hope to recruit more student and post-doctoral fellows to work on this project,” Dr. Kim said.
Originally published at Today@Wayne.
