Combined CB2 receptor agonist and photodynamic therapy synergistically inhibit tumor growth in triple negative breast cancer

Abstract

Triple negative breast cancer (TNBC) is the deadliest form of breast cancer because it is more aggressive, diagnosed at later stage and more likely to develop local and systemic recurrence. Many patients do not experience adequate tumor control after current clinical treatments involving surgical removal, chemotherapy and/or radiotherapy, leading to disease progression and significantly decreased quality of life. Here we report a new combinatory therapy strategy involving cannabinoid-based medicine and photodynamic therapy (PDT) for the treatment of TNBC. This combinatory therapy targets two proteins upregulated in TNBC: the cannabinoid CB2 receptor (CB₂R, a G-protein coupled receptor) and translocator protein (TSPO, a mitochondria membrane receptor). We found that the combined CB₂R agonist and TSPO-PDT treatment resulted in synergistic inhibition in TNBC cell and tumor growth. This combinatory therapy approach provides new opportunities to treat TNBC with high efficacy. In addition, this study provides new evidence on the therapeutic potential of CB₂R agonists for cancer.

Keywords: Agonist; CB2 receptor; Cannabinoid; Combination therapy; Photodynamic therapy; Synergistic; Triple negative breast cancer.