A research team led by Yibin Kang, the Warner-Lambert/Parke-Davis Professor of Molecular Biology at Princeton University, has identified a new approach that could lead to cancer treatments targeting retinoid metabolism. Their findings address longstanding questions about the relationship between vitamin A derivatives and cancer.
Retinoids are metabolites produced when the body breaks down vitamin A. Decades ago, all-trans retinoic acid (ATRA), a type of retinoid, was used successfully in combination with arsenic to treat acute promyelocytic leukemia (APL). This led to public interest in vitamin A-rich foods as potential cancer therapies. However, subsequent clinical trials found that vitamin A or retinoids often promoted tumor growth rather than reducing it, except in patients with APL. As a result, the U.S. Food and Drug Administration increased scrutiny of such treatments and limited their approval to specific cases.
Kang’s group has now clarified why most cancers do not respond positively to retinoid-based therapies. Over ten years of research revealed that while APL is responsive to ATRA and arsenic treatment, other cancers use retinoids to evade immune detection.
The researchers focused on an enzyme involved in producing retinoic acid and screened for compounds that could inhibit its activity without disrupting overall vitamin A metabolism. They identified KyA33 as a molecule capable of blocking this pathway at a critical step without causing harmful side effects related to vision loss.
According to their recent publication in Nature Immunology, first author Cao Fang—who completed her Ph.D. at Princeton in 2025—demonstrated how KyA33 suppresses retinoic acid production both in cancer cells and dendritic cells within the immune system. The compound enhanced the effectiveness of dendritic cell vaccines in animal studies and may also function as an independent immunotherapy for cancer.
“By targeting these enzymes that produce a localized high concentration of retinoic acid in tumors, our compounds have the potential to reactivate important immune responses to cancer,” said Kang.
In addition to their academic work, Kang and former graduate student Mark Esposito have established Kayothera, a startup aiming to develop advanced versions of KyA33 for clinical use through regulatory pathways.
“This whole process is a very good example of how academic research in the lab can identify leads and targets that ultimately support a successful biotech company,” said Kang.
The research received funding from organizations including the Ludwig Institute for Cancer Research, Brewster Foundation, Susan Komen Foundation, Metavivor Breast Cancer Research, Breast Cancer Research Foundation, American Cancer Society, New Jersey Health Foundation, and National Science Foundation.
