Canagliflozin in combination with standard therapy to improve the treatment of unresected prostate cancer

Abstract

Prostate cancer (PrCa) is a leading cause of cancer-related death in men worldwide. Standard treatments for unresected PrCa include radiation therapy, androgen deprivation or anti-androgen therapies. However, many patients develop resistance to these therapies indicating a need for a new treatment that can enhance their therapeutic efficacy. Our studies show a promising new strategy to achieve this task using canagliflozin, an FDA-approved medication currently used to treat diabetes, kidney and heart failure. We found that canagliflozin interrupts cellular energy production, inhibits biosynthetic pathways and improves the efficacy of radiotherapy in radiation naïve and radio-resistant human PrCa models. In addition, we found that canagliflozin has promising anti-androgen activity by reducing the protein levels and the activity of androgen receptor (AR) in PrCa cells and tumors both alone and in combination with commercially available anti-androgens. These promising findings suggest that canagliflozin could be used in combination with current standard-of-care therapies for the treatment of PrCa. Given that canagliflozin is an approved medication, tolerated well by diabetic and non-diabatic individuals, the work presented here generates a basis for rapid investigation of this new treatment in early phase clinical trials.