ATRA Improves the Anti-tumor Effect of Photodynamic Therapy. Anti-carcinoma effects of ATRA+PDT

The vitamin A metabolite all-trans retinoic acid (ATRA) has anti-cancer potential; however, a lack of clinical success has prevented its approval for solid tumors. Herein, we propose combining low-dose ATRA preconditioning with fimaporfin-based photodynamic therapy (ATRA+PDT) to treat of solid cancers. Compared to PDT or ATRA monotherapy, ATRA+PDT resulted in growth inhibition and reduced cell viability in 5 different carcinoma cell lines. In human HT-29 colon adenocarcinoma cells, the effect of ATRA+PDT on gene transcription was evaluated using high-throughput next-generation RNA sequencing (RNA-seq). Pathway analysis indicated increased apoptosis after ATRA+PDT compared to PDT, confirming the TUNEL data, and identified the unfolded protein response (UPR) as activated. During the first 20 days post-ATRA+PDT, we obtained significant anti-tumor responses in HT-29 xenografts, including complete responses in 2/5 animals. In conclusion, ATRA+PDT represents a promising novel combination strategy for the treatment of solid tumors.