When combined, a novel LSD1 inhibitor and an existing therapy enhance each other’s anti-cancer effects

SmartState Endowed Chair in Drug Discovery Pat Woster and his research team have developed novel compounds that show early promise at fighting the rare pediatric cancer neuroblastoma when paired with the existing anti-cancer drug bortezomib (Velcade, Takeda Oncology). The novel compounds block or inhibit an enzyme known as lysine-specific demethylase 1 (LSD1). The MUSC team reports its findings in the European Journal of Medicinal Chemistry.

“Our compounds are a new chemical class of LSD1 inhibitors and are the first small molecules to produce a synergistic anti-tumor response in combination with bortezomib,” said Woster, who is head of the Department of Drug Discovery and Biomedical Sciences at MUSC.

Such combination therapies are the way of the future, said co-author Yuri Peterson, Ph.D. Peterson is assistant director of the Drug Discovery Core and director of Bioenergetics Profiling at MUSC.

“Drug development in cancer therapeutics is moving away from single toxic agents to specific combinations that are personalized according to the patient’s genetics,” said Peterson. “By using these combined therapies, we can increase the positive effect while limiting the negative effects of cancer-killing agents like bortezomib.”

Such new treatment options are urgently needed for children with high-risk disease. Current therapies are often ineffective and incredibly painful. Nearly half of these children die within five years of diagnosis.

The Woster team is keenly aware of the challenges faced by these children and motivated to provide them new options.

“We need treatments that are not only more effective against high-risk disease but that are better tolerated by patients,” said postdoctoral scholar Catherine Mills, Ph.D., first author of the article.

Read the full story by Jaclyn Dunne in the MUSC News Center.