Enhancing Photodynamyc Therapy Efficacy by Combination Therapy: Dated, Current and Oncoming Strategies

Abstract

Combination therapy is a common practice in many medical disciplines. It is defined as the use of more than one drug to treat the same disease. Sometimes this expression describes the simultaneous use of therapeutic approaches that target different cellular/molecular pathways, increasing the chances of killing the diseased cell. This short review is concerned with therapeutic combinations in which PDT (Photodynamyc Therapy) is the core therapeutic partner. Besides the description of the principal methods used to assess the efficacy attained by combinations in respect to monotherapy, this review describes experimental results in which PDT was combined with conventional drugs in different experimental conditions. This inventory is far from exhaustive, as the number of photosensitizers used in combination with different drugs is very large. Reports cited in this work have been selected because considered representative. The combinations we have reviewed include the association of PDT with anti-oxidants, chemotherapeutics, drugs targeting topoisomerases I and II, antimetabolites and others. Some paragraphs are dedicated to PDT and immuno-modulation, others to associations of PDT with angiogenesis inhibitors, receptor inhibitors, radiotherapy and more. Finally, a look is dedicated to combinations involving the use of natural compounds and, as new entries, drugs that act as proteasome inhibitors.

Comparison of caspase-3 activation in tumor cells upon treatment of chemotherapeutic drugs using capillary electrophoresis

“…The advantages of using combination therapy appear to lie in its combined targeting ability to different signal transduction pathways and enhanced approaches for combating drug resistance (Postiglione et al, 2011). Richard (Hara et al, 2005) reported that combination of low concentrations of TNF (1×10 2 IU/mL) and cisplatin has no obvious effects on caspase-3 activation.…”

Biophotonic techniques for manipulation and characterization of drug delivery nanosystems in cancer therapy

“…However, the clinical use of PDT is still limited due to several issues. One approach which is being explored for the enhancement of the effectiveness of PDT involves the combination of a different therapeutic modality, such as surgery, chemotherapy and radiotherapy [25][26][27]. During the last twenty years of research, radiotherapy (based on the use of ionizing radiation) has been combined with PDT (based on the use of non-ionizing radiation), although conflicting results have been reported [28][29][30][31].…”

Photonanomedicine: a convergence of photodynamic therapy and nanotechnology

“…Such mechanistically non-overlapping combinations of PDT with chemotherapy could overcome chemoresistance and potentially exert a synergistic effect in stubbornly refractive tumors. 156, 193, 212 Duska et al used the F(ab′) 2 fragment of OC-125 conjugated to a cationic poly-lysine polymer that was modified with multiple chlorin e6 (Ce6) PS molecules. 194, 208 This PIC was assessed in 5 human cancer cell lines as well as 19 primary cultures obtained from solid tumors and ascites samples derived from platinum-responsive and platinum-resistant OvCa patients.…”