A class of experimental cancer drugs called BET inhibitors have shown promise for treating cancers of the blood but can induce toxic side effects.
In a new study, researchers have found a new drug that in animal studies demonstrates greater potency against a wider variety of cancers, as well as against solid tumors, and also produces fewer side effects compared to others in the class.
The research was conducted by Yale scientists.
Current BET-inhibiting small molecule drugs in development—numerous trials are underway—have only been effective against blood cancers such as multiple myeloma and leukemia.
They have been ineffective for most solid tumors, such as those found in brain cancer, breast cancer, and ovarian cancer.
And these drugs have toxic side effects, including fatigue, nausea, loss of taste, and low platelet counts.
In animal studies, the Yale researchers examined the impact of the new inhibitor, called NHWD-870, on ovarian cancer, small cell lung cancer, breast cancer, lymphoma, and melanoma.
They found it was between three times and 50 times more potent against cancer cells than existing BET inhibitors.
Unlike other BET inhibitors, NHWD-870 exhibited robust activity against solid tumors, partly by preventing tumor-associated macrophages (TAMs), or large white blood cells in the immune system, from proliferating.
TAMs act as a support system for tumor cells, suppressing anti-tumor activity, and facilitating tumor regrowth after treatment.
The impact of the inhibitor on TAMs was significant, preventing the large white blood cells from spreading and restricting tumor growth.
NHWD-870 also had lower toxicity, as measured in body weight loss in animals, than other inhibitors.
The team says these findings not only uncover the importance of the target BRD4, but also reveal how it functions to regulate the tumor micro-environment.
The team is now pursuing clinical trials in humans. With colleagues at Yale and other collaborators, they will test the effectiveness of NHWD-870 on melanoma and ovarian cancer patients.
The lead author of the study is Qin Yan, an associate professor of pathology and director of the epigenetics program.
The study is published in Nature Communications.
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