The role of photodynamic therapy on multidrug resistant breast cancer

Abstract

Breast cancer heterogeneity allows cells with different phenotypes to co-exist, contributing to treatment failure and development of drug resistance. In addition, abnormal signal transduction and dysfunctional DNA repair genes are common features with breast cancer resistance. Chemo-resistance of breast cancer associated with multidrug resistance events utilizes ATP-binding cassette (ABC) efflux transporters to decrease drug intracellular concentration. Photodynamic therapy (PDT) is the treatment that involves a combination of a photosensitizer (PS), light and molecular oxygen to induce cell death. This treatment modality has been considered as a possible approach in combatting multidrug resistance phenomenon although its therapeutic potential towards chemo-resistance is still unclear. Attempts to minimize the impact of efflux transporters on drug resistance suggested concurrent use of chemotherapy agents, nanotechnology, endolysosomal release of drug by photochemical internalization and the use of structurally related compound inhibitors to block the transport function of the multidrug resistant transporters. In this review, we briefly summarize the role of membrane ABC efflux transporters in therapeutic outcomes and highlight research findings related to PDT and its applications on breast cancer with multidrug resistance phenotype. With the development of an ideal PS for photodynamic cancer treatment, it is possible that light activation may be used not only to sensitize the tumour but also to enable release of PS into the cytosol and as such bypass efflux membrane proteins and inhibit escape pathways that may lead to resistance.