Redaporfin Development for Photodynamic Therapy and its Combination with Glycolysis Inhibitors
Maria Inês P Mendes1, Luis G Arnaut1
1CQC-IMS, Department of Chemistry, University of Coimbra, Coimbra, Portugal.
Abstract:
Photodynamic therapy (PDT) remains an underutilized treatment modality in oncology. Many efforts have been dedicated to the development of better photosensitizers, better formulations and delivery methods, rigorous planning of light dose distribution in tissues, mechanistic insight, improvement of treatment protocols and combinations with other therapeutic agents. Hopefully, progress in all these fields will eventually expand the use of PDT. Here we offer a brief review of our own contribution to the development of a photosensitizer for PDT - redaporfin - currently in Phase II clinical trials, and present data on its combination with two glycolysis inhibitors: 2-deoxyglucose and 3-bromopyruvate. We show that 3-bromopyruvate is more cytotoxic to a carcinoma cell line (CT26) than to a normal fibroblast (3T3) cell line, and that this selectivity is maintained in the in vitro combination with redaporfin-PDT. This combination was investigated in BALB/c mice with large subcutaneous CT26 tumors and it is shown that the cure rate in the combination is higher (33% cures) than in PDT (11% cures) or in 3-bromopyruvate (no cures) alone. The combination of redaporfin-PDT with 3-bromopyruvate illustrates the potential of combination therapies and how PDT benefits can be enhanced by systemic drugs with complementary targets.
Insights
Combining redaporfin-photodynamic therapy (PDT) with 3-bromopyruvate enhances cancer treatment. This combination therapy shows improved cure rates for carcinoma tumors compared to PDT or 3-bromopyruvate alone.
Area of Science:
- Oncology
- Photochemistry
- Biochemistry
Background:
- Photodynamic therapy (PDT) is an underutilized cancer treatment.
- Developing improved photosensitizers, formulations, and treatment protocols can expand PDT's use.
- Redaporfin is a novel photosensitizer currently in Phase II clinical trials.
Purpose of the Study:
- To evaluate the combination of redaporfin-PDT with glycolysis inhibitors.
- To assess the efficacy of combining redaporfin-PDT with 2-deoxyglucose and 3-bromopyruvate.
- To investigate the synergistic effects of redaporfin-PDT and 3-bromopyruvate in a preclinical cancer model.
Main Methods:
- In vitro cytotoxicity assays using carcinoma (CT26) and fibroblast (3T3) cell lines.
- In vivo studies in BALB/c mice bearing subcutaneous CT26 tumors.
- Combination therapy involving redaporfin-PDT and 3-bromopyruvate.
Main Results:
- 3-bromopyruvate demonstrated selective cytotoxicity against CT26 cells compared to 3T3 cells.
- This selectivity was maintained when combined with redaporfin-PDT in vitro.
- Combination therapy achieved a 33% cure rate in mice, significantly higher than PDT (11%) or 3-bromopyruvate (0%) alone.
Conclusions:
- The combination of redaporfin-PDT and 3-bromopyruvate shows significant therapeutic potential.
- Systemic drugs targeting complementary pathways can enhance PDT efficacy.
- This combination therapy strategy warrants further investigation for improved cancer treatment outcomes.
