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.

Photodynamic therapy (PDT) is a treatment modality that involves three components: combination of a photosensitizer, light and molecular oxygen that leads to localized formation of reactive oxygen species (ROS). The ROS generated from this promising therapeutic modality can be lethal to the cell and leads to consequential destruction of tumor cells. However, sometimes the ROS trigger a stress response survival mechanism that helps the cells to cope with PDT-induced damage, resulting in resistance to the treatment. One preferred mechanism of cell death induced by PDT is apoptosis, and B-cell lymphoma 2 (Bcl-2) family proteins have been described as a major determinant of life or death decision of the death pathways. Apoptosis is a cellular self-destruction mechanism to remove old cells through the biological event of tissue homeostasis. The Bcl-2 family proteins act as a critical mediator of a life–death decision of cells in maintaining tissue homeostasis. There are several reports that show cancer cells developing resistance due to the increased interaction of the pro-survival Bcl-2 family proteins. However, the key mechanisms leading to apoptosis evasion and drug resistance have not been adequately understood. Therefore, it is critical to understand the mechanisms of PDT resistance, as well as the Bcl-2 family proteins, to give more insight into the treatment outcomes. In this review, we describe the role of Bcl-2 gene family proteins’ interaction in response to disease progression and PDT-induced resistance mechanisms.

Photodynamic therapy (PDT) is currently enjoying considerable attention as the subject of experimental research to treat resistant cancers. The preferential accumulation of a non-toxic photosensitizer (PS) in different cellular organelles that causes oxidative damage by combining light and molecular oxygen leads to selective cell killing. However, one major setback, common among other treatment approaches, is tumor relapse and the development of resistance causing treatment failure. PDT-mediated resistance could result from increased drug efflux and decreased localization of PS, reduced light exposure, increased DNA damage repair, and altered expression of survival genes. This review highlights the essential insights of PDT reports in which PDT resistance was observed and which identified some of the molecular effectors that facilitate the development of PDT resistance. We also discuss different perceptions of PDT and how its current limitations can be overturned to design improved cancer resistant treatments.

Introduction: Globally, breast cancer is the most common life-threatening malignant disease among women. Adjuvant chemotherapeutic treatment of anthracycline-based chemotherapy (e.g., doxorubicin) has been shown to be more advantageous over non-anthracycline-based therapies, yet possess the tenacity of developing resistance and potential side effects which have limited its use in the clinical setting. These reasons necessitate combining doxorubicin with emerging photodynamic treatment regimens. Areas covered: In this review, the authors have concisely explained doxorubicin chemotherapy and the photobiological processes of phthalocyanine triggered photodynamic therapy (PDT). A literature search was conducted and reports demonstrating the use of doxorubicin and photodynamic therapy as a treatment modality for breast cancer were identified. More emphasis was made on studies demonstrating the efficacy and improved anticancer effect of combining chemotherapy with photodynamic therapy. However, it was concluded that for this combination therapy, still in it’s infancy, it could be relevant when integrated into standard treatment. Expert Commentary: To these effects, comprehensive models based on experimental evaluations are needed for rational design of anthracycline-based chemotherapy and PDT to be integrated into the clinical setting.

Punica granatum (P. granatum) is a fruit-bearing tree from the Punicaceae family, indigenous to Iran. This plant has healing qualities that have drawn the interest of the medical community as an alternative treatment for malignancies and non-malignancies. Its healing quality is due to the phytochemicals present in the plant. These include ellagic acid, punicic acid, phenols, and flavonoids. In traditional medicine, P. granatum has been used in treating diseases such as dysentery, bleeding disorders, leprosy, and burns. This review explores the effects of the phytochemical constituents of P. granatum on photodynamic therapy for cancer, chronic inflammation, osteoarthritis, and viral infections. Its antioxidant and antitumor effects play a role in reduced free radical damage and cancer cell proliferation. It was concluded that P. granatum has been used for many disease conditions for a better therapeutic outcome. This paper will give visibility to more studies and expand the knowledge on the potential use of P. granatum in photodynamic cancer treatment.