A new project funded in part by the Wisconsin Partnership Program is aiming to improve treatment and health outcomes for women living with triple-negative breast cancer (TNBC), an aggressive type of cancer that has few effective treatments.
TNBC can strike anyone but occurs more often in younger women, African American and Hispanic women and women who have the BRCA1 gene mutations. Women with metastatic TNBC have a poor prognosis due to the lack of alternatives to chemotherapy.
The project, Metabolic Priming Triple-Negative Breast Cancer to Proapoptotic Therapy is exploring metabolic priming, a novel model for cancer therapy that uses dietary manipulations to make cancer cells more vulnerable to a targeted new drug that kills tumor cells, but not normal cells. The study is the first of its kind to use diet to prime triple-negative breast cancer cells to respond to a targeted cancer drug.
Led by Vincent Cryns, MD, professor of medicine at the UW School of Medicine and Public Health, the project brings together a multidisciplinary team of scientists and clinicians with broad expertise in cancer biology, clinical trials, nutrition, metabolism and biostatistics. The team will explore whether reducing dietary intake of the nutrient methionine, which is abundant in meats, fish, eggs and some nuts but is generally low in vegetables and fruits, can improve a patient’s response to the drug ONC201.
Hollman says, “For many years I avoided thinking about my cancer experience, but eventually admitted to myself that it was part of me and something I shared with a community of survivors. By becoming an advocate, I can reach out to other members of this community and ensure that the patient’s perspective comes through all phases of the study.” She says, “As breast cancer survivors, our group is acutely aware of the urgent need for better treatments.”
Cryns’ group has shown that reducing methionine increases the ability of ONC201 to trigger tumor cells to die. The novel approach has the potential to dramatically improve clinical outcomes in metastatic TNBC by specifically targeting chemotherapy-resistant cancer stem cells that contribute to treatment resistance. The team also receives invaluable input from a team of breast cancer survivors, who serve as project advocates. (see sidebar)
In the study, patients with metastatic TNBC are randomly assigned to a diet low in methionine, or a regular diet followed by ONC201. Patients on the low-methionine diet will consume fruits and vegetables as well as a medical protein supplement shake that contains all essential amino acids except methionine.
“One advantage of this treatment is that it should cause fewer side effects than chemotherapy,” says Cryns. “The patients in our study have already had to endure the side effects of multiple chemotherapy drugs, which were unable to control their metastatic disease.”
If successful, the study will move to a large-scale clinical trial for validation. “Ultimately, we hope our findings will have a significant impact on the quality of life and survival of women living with triple-negative breast cancer,” says Cryns.
