|Xingming Deng--Courtesy of the Winship Cancer Institute at Emory University|
The Bcl-2 protein has long been a target in cancer drug R&D. The protein plays a key role in preventing cell death, or apoptosis, and AbbVie ($ABBV) has been working on an inhibitor--the "breakthrough therapy" venetoclax--that could be used in combination with other therapies to strip this defense mechanism against a range of cancers.
Now, investigators at the Winship Cancer Institute at Emory University say they've found a new molecule that appeared to do better than an inhibitor in preclinical in vivo testing. They've been working on a molecule that specifically targets the BH4 domain of Bcl-2, "converting it from a survival molecule to a cell death inducer," according to the team's study, published in Cancer Cell.
"Discovery of the Bcl2 BH4 antagonist as the way to promote cancer cell death may provide a new weapon against lung cancer," says lead author Xingming Deng, an associate professor in Emory's Department of Radiation Oncology.
Their drug is dubbed BDA-366, which they say can suppress growth of lung cancer xenografts derived from cell lines and patients without toxicity when used at an "effective" dose. "mTOR inhibition upregulates Bcl2 in lung cancer cells and tumor tissues from clinical trial patients," they write in their abstract. "Combined BDA-366 and RAD001 treatment exhibits strong synergy against lung cancer in vivo."
"We are now testing this molecule further in preparation for future testing among eligible patients," says co-author Walter Curran, the executive director of the institute.
- here's the release
- read the research abstract