Targeting Metabolic Vulnerability: Fasting Mimicking Diets and TNBC Sensitization

Triple-negative breast cancer (TNBC) is a challenging subtype to treat due to its aggressive nature and lack of targeted hormonal receptors. However, emerging research suggests that the metabolic landscape of TNBC may be its "Achilles’ heel."

In this interview, Ifeoma Dikeocha, PhD, spoke with CancerNetwork® and discussed the synergistic potential of fasting mimicking diets (FMD) when paired with standard-of-care chemotherapy. Dikeocha explored the mechanistic rationale behind why metabolic restriction—specifically the reduction of circulating glucose, insulin, and IGF-1—sensitizes TNBC cells to cytotoxic agents like doxorubicin and cyclophosphamide. By exploiting the inherent metabolic vulnerabilities of this subtype, FMD represents a promising adjunctive strategy to enhance therapeutic index and improve survival outcomes.

Dikeocha is a PhD candidate from the University of Adelaide.

Transcript:

Basically, triple-negative breast cancer, repeatedly, shows strong sensitization signals on the metabolic restriction, and this is very well seen when this metabolic procedure is combined with chemotherapy. In our study, and in the preclinical studies fasting mimicking diet when combined with and agent like doxorubicin and cyclophosphamide, would reduce tumor growth and it improves survival. From the literature, we saw that triple-negative models.

When we think about it mechanistically, the rationale was while triple-negative breast cancer may be more responsive, it also aligns with the other vulnerabilities that dietary interventions, like fasting mimicking diets are designed to exploit. Essentially reducing circulating glucose, also reducing insulin and IGF-1, that’s insulin-like growth factor 1, which basically, reduces apoptosis, and slows down inflammation in the system as well. In summary, we can say that triple-negative breast cancer appears to be a metabolically vulnerable subtype and diets like fasting mimicking diets or calorie restriction, can exploit this vulnerability, and especially when chemotherapy is introduced, this would then enhance the treatment responses.

Reference

Dikeocha IJ, Wardill HR, Coller JK, Bowen JM. Dietary interventions and tumor response to chemotherapy in breast cancer: A comprehensive review of preclinical and clinical data. Clin Nutr ESPEN. 2024;63:462-475. doi:10.1016/j.clnesp.2024.06.048