News : 2019 : April

Vitamin C Makes this Emerging Breast Cancer Therapy Safer, More Effective

Using an inexpensive, over-the-counter supplement, researchers at the University of Miami may have rescued an emerging breast cancer therapy from what could have been insurmountable toxicity issues.

How useful is a cancer drug if it makes patients so sick they are forced to stop treatment? Not very.

That is why it is essential to get highly deleterious or even life-threatening side effects under control. Toxicity problems are encountered frequently in drug development.

Fortunately, this new study by University of Miami researchers has shown that vitamin C can make triple negative breast cancer (TNBC) cells more sensitive to new antitumor compounds called “BET inhibitors” or “BETi,” which have proven difficult to tolerate at doses that are high enough to kill stubborn cancer cells.

“Our findings show that adding vitamin C makes cancer cells more vulnerable to these particular compounds,” said senior author Dr. Gaofeng Wang, a primary member of the John P. Hussman Institute for Human Genomics (HIHG), and an Associate Professor in the Dr. John T. Macdonald Foundation Department of Human Genetics. Dr. Wang is also a member of the Sylvester Comprehensive Cancer Center (SCCC). “That means lower doses can be used. Lower doses tend to be less toxic and causes fewer side effects.”

About 10%-20% of breast cancer patients have the TNBC type. Triple negative breast cancer typically occurs at younger ages (ages 40-50) and among African American and Hispanic women or those with BRCA1 mutations. Compared to other breast cancers, TNBC is particularly aggressive and likely to reoccur following standard treatment, which often involves a combination of therapies, such as surgery, radiation therapy, and chemotherapy.

BET inhibitors are a promising treatment option now under development. When administered at the right doses, they can be very effective against TNBC cells. Multiple clinical trials are currently evaluating their usefulness. The major drawback has been serious side effects, such as gastrointestinal toxicity, anemia (a lack of healthy red blood cells), thrombocytopenia (low blood platelets), neutropenia (inadequate neutrophils – a type of white blood cell), diarrhea, fatigue, and nausea. These side effects, which have shown up in phase-I clinical trials, are threatening the viability of BET inhibitors in patient care. Cancer drugs can only work if patients are able to tolerate them at effective doses.

The UM researchers on this study, all from the Miller School of Medicine, used a method for scientific experimentation called high-throughput screening to assess how the addition of vitamin C would impact the efficacy of BET inhibitors. Their article, which appears in the journal EBioMedicine, concludes that supplementing these “promising yet toxic cancer drugs” with vitamin C might expand their utility and decrease the severity of their side effects.

“We are so pleased to have found a simple, elegant solution that may allow this emerging cancer drug to work better,” said Dr. Wang. “That doesn’t happen every day.”

Dr. Wang’s lab seeks to identify how environmental factors affect the epigenome in ways that are relevant to cancer treatment. In 2018, his group found that vitamin C promotes apoptosis (programmed cell death) in breast cancer cells.

The other collaborators on this study are Drs. Sushmita Mustafi, Vladimir Camarena, Rehana Qureshi, Hyunho Yoon, Claude-Henry Volmar, Tyler C. Huff, David W. Sant, Lihong Zheng, Shaun P. Brothers, Claes Wahlestedt, and Joyce Slingerland.

Those interested in vitamin C’s role in preventing or treating breast cancer should consult with a healthcare provider. In certain people, especially those with kidney problems, high doses of vitamin C can be dangerous. For reference, the recommended daily amount of vitamin C is 75 mg for healthy adult women and 90 mg for healthy adult men. One medium-sized orange provides about 70 mg of vitamin C. Cancer patients may require much more vitamin C supplementation.

Journal article:

S.Mustafi, V. Camarena, R. Qureshi, et al., Vitamin C supplementation expands the therapeutic window of BETi for triple negative breast cancer, EBioMedicine, https://doi.org/10.1016/j.ebiom.2019.04.006