Photodynamic therapy (PDT) has emerged as a potential therapeutic option for most localized cancers. Its high measure of specificity and minimal risk of side effects compared to other therapies has put PDT on the forefront of cancer research in the current era. The primary cause of treatment failure and high mortality rates is the occurrence of cancer resistance to therapy. Hence, PDT is designed to be selective and tumor-specific. However, because of complex biological characteristics and cell signaling, cancer cells have shown a propensity to acquire cellular resistance to PDT by modulating the photosensitization process or its products. Fortunately, nanotechnology has provided many answers in biomedical and clinical applications, and modern PDT now employs the use of nanomaterials to enhance its efficacy and mitigate the effects of acquired resistance. This review, therefore, sought to scrutinize the mechanisms of cellular resistance that affect the therapeutic response with an emphasis on the use of nanomaterials as a way of overriding cancer cell resistance. The resistance mechanisms that have been reported are complex and photosensitizer (PS)-specific. We conclude that altering the structure of PSs using nanotechnology is an ideal paradigm for enhancing PDT efficacy in the presence of cellular resistance.

The heterogeneous nature of cancer puts cancer stem cells (CSCs) at the beating heart of the tumour. Because of their inherent characteristics of stemness, CSCs evade putative cancer therapies, resulting in treatment resistance or tumour recurrence after a seemingly successful treatment. To prevent treatment resistance and cancer recurrence, killing the beating heart of the tumour is of utmost importance. This study therefore, sought to determine the effect of Photodynamic Therapy (PDT) in eradicating cervical cancer and cervical CSCs. Cervical CSCs were isolated from a cervical adenocarcinoma cell line, HeLa cells, and grown in liquid medium incubated at 37° C, 5% CO 2 and 85% humidity. Increasing doses of AlPcS mix photosensitizer were administered to both the total cell population and the isolated CSCs, and irradiated using 673.2 nm diode laser. Post-irradiation cellular changes were observed using biochemical assays and microscopy to determine the response of both the total cell population and the CSCs. Results showed a dose-dependent response of both cell populations to treatment, by demonstration of significant morphologic changes, increased cytotoxicity, and decreased cell viability and proliferation. The study suggested that PDT using AlPcS mix is a very effective treatment method for the eradication of cervical cancer cells and cervical CSCs, in vitro .

Good medicine is based on good science, inquiry driven and open to new paradigms. For a complex disease such as cancer, a complex treatment regime that is well structured and multifactorial is indispensable. In the present day, Complementary and Alternative Medicine (CAM) therapies are being used frequently for cancer, alongside modern biological therapies and allopathic medicine, in what is called integrative oncology. In all conscience, the use of natural, less invasive interventions whenever possible is ideal. However, a comprehensive understanding of not only the etiopathology of individual cancers, but also the detailed genetic and epigenetic characteristics, the cancer hallmarks, that clearly show the blueprint of the cancer phenotype is a requisite. Different tumors have a common behavioral pattern, but their specific features at the genetic and epigenetic levels vary to a great extent. Henceforth, with so many failed attempts to therapy, drug formulations and combinations need a focused pre-assessment of the inherent features of individual cancers to destroy the tumors holistically by targeting these features. This review therefore presents innocuous therapeutic regimes by means of CAM and integrative medicine approaches that can specifically target the hallmarks of cancer, using the case of cervical cancer.

Cancer is a global burden that has prompted extensive research into prevention and treatment, over many decades. Scientific studies have shown that subset of cells within a tumour, known as cancer stem cells (CSCs), are responsible for tumourigenesis, metastasis, drug resistance, and recurrences. CSCs have characteristic features of enhanced self-renewal, proliferation, and limited but multidirectional differentiation capacity. The discovery of CSCs has initiated extensive research into novel cancer treatment regimes. Evidence indicates that CSCs are resistant to conventional chemo- and radiation therapy leading to treatment failures, cancer metastasis, secondary cancer formation, and relapse. Because of the observed phenomena in the course of cancer prognosis, a need for treatment modalities targeting CSCs is important. Photodynamic therapy (PDT) is a clinically approved, minimally invasive, therapeutic procedure that can exert a selective cytotoxic activity toward cancerous cells while reducing toxicity to normal cells. It uses a photosensitizer (PS) that becomes excited when subjected to light at a specific wavelength, and the PS forms reactive oxygen species (ROS) killing malignant cells. Currently, PDT is being investigated as a target specific treatment for CSCs by the addition of carrier molecules and antibody conjugates bound to the PS. Targeted PDT (TPDT) may be able to not only eradicate the tumour mass but kill CSCs as well.

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