Using the “reverse Warburg effect” to identify high-risk breast cancer patients

Ethanol exposure induces the cancer-associated fibroblast phenotype and lethal tumor metabolism

“…[29][30][31][32][33][34][35][36][37][38][39] Similarly, elevated MCT4 in cancer-associated fibroblasts is predictive of a poor clinical outcome in breast cancer patients, and strictly correlates with a loss of Cav-1. 40 Thus, our current results with co-culture directly mirror what occurs in a specific subset of high-risk human breast cancers in patients in vivo. Perhaps, more importantly, our current results imply that alcohol consumption in women with breast cancer can affect their tumor's biomarker status, shifting it from Cav-1(+)/ MCT4(-)/ER(+) to Cav-1(-)/MCT4(+)/ER(-), which would be strongly predicted to negatively affect clinical outcome.…”

Mitochondrial dysfunction in breast cancer cells prevents tumor growth

“…A loss of stromal Cav-1 and an upregulation of stromal MCT4 are markers of oxidative stress associated with poor clinical outcome in breast cancer. [34][35][36][37][38][39][40][41][42] Figure 3A and B shows that fibroblasts overexpressing UCP1, UCP2 and UCP3 all induce the downregulation of Cav-1 expression and increase MCT4 levels, as compared with control cells.…”

“…These studies also validate the "two-compartment tumor metabolism" model of tumorigenesis. 21,[27][28][29][30][31][32][33][34] …”

Ketone body utilization drives tumor growth and metastasis

“…In breast cancer patients, a loss of stromal Cav-1 expression is associated with increased tumor recurrence, metastasis, drug resistance and overall poor clinical outcome. [10][11][12][13] Thus, stromal Cav-1 could be used as a biomarker to select patients that would be more likely to benefit from therapy with ketone inhibitors, allowing biomarker-based treatment stratification and personalized cancer therapy.…”