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Inhibition of DGAT for the treatment of cancer

Healthcare Portfolios
Oncology
College
College of Medicine (COM)
Researchers
Guo, Deliang
Licensing Manager
Ezzell, Janel ezzell.11@osu.edu

T2020-075

Background

Dysregulated fat metabolism is an established hallmark of cancer cells. However, the disruption of lipid homeostasis in cancer cells remains an elusive target for therapy. Diacylglycerol-acyltransferase (DGAT) regulates the final and committed step for triglyceride synthesis. There are two known isoforms of the enzyme, DGAT 1 and DGAT 2. Due to their well-established role in lipid metabolism, several isoform-specific inhibitors have been the focus of industry sponsored clinical pipelines for various metabolic diseases, such as obesity, dyslipidemia, and fatty liver disease. However, the effects of DGAT inhibition in various cancer types are poorly understood.

Technology

Researchers at The Ohio State University, led by Dr. Deliang Guo, have discovered a novel therapeutic strategy targeting DGAT in cancer. They have demonstrated DGAT plays a critical role in regulating lipid homeostasis and protecting cancer cells from oxidative damage induced by excess fatty acids. Importantly, DGAT isoforms are differentially regulated in different cancer types, and inhibiting DGAT induces dramatic cell apoptosis and reduction of tumor growth in vitro and in vivo. Upon screening a multitude of cancer types, Dr. Guo’s team has discovered a novel therapeutic approach for liver cancer. Dr. Guo's studies uncover previously unrecognized molecular mechanisms regulating lipid homeostasis in cancer and offer a promising new approach for hepatocellular carcinoma therapy.

Benefits/Advantages

  • Leverages clinical candidates currently in Phase II clinical trials
  • Novel cancer therapeutic target
  • Validated target for dyslipidemia

Stage of Development

  • Pre-clinical
  • in vitro and in vivo studies

Intellectual Property

  • Provisional Patent Application Filed