Resistance to Photodynamic Therapy in Cancer (Resistance to Targeted Anti-Cancer Therapeutics Book 5)

This volume provides a comprehensive review of resistance induced by photodynamic therapy (PDT) in tumor cells. Understanding the underlying mechanisms in this process leads to the improvement of therapeutic modality, in combination with chemotherapy, immunotherapy, and radiotherapy. Photodynamic therapy is a minimally invasive therapeutic procedure that can exert a selective or preferential cytotoxic activity toward malignant cells. The procedure involves administration of an intrinsically non-toxic photosensitizing agent (PS) followed by irradiation at a wavelength corresponding to a visible absorption band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Studies reveal that PDT can be curative, particularly in early stage tumors and this volume explores the potential of PDT, but also reveals strategic approaches to overcome resistance in tumor cells. Direct Autophagy Inhibition via Photosensitizers: An Untapped Potential?Autophagy Pathways In Vivo and PDT Therapy Response: Uncharted Territories; Autophagy-Based Suppression of Anti-Cancer Immunity: An Emerging Paradigm in PDT Therapy Response; Conclusion; References; Chapter-5; Isolation and Initial Characterization of Resistant Cells to Photodynamic Therapy; Introduction; Isolation of PDT-Resistant Cells; Defining the Level of Resistance; Selecting the Cellular Model; Strategies for Selection of Resistant Cells; In Vitro Selection; In vivo Selection; Examples of PDT Selection Preface; Contents; Contributors; Part I; Introduction; Chapter-1; Basic and Clinical Aspects of Photodynamic Therapy; Introduction; Basic Aspects of Photodynamic Therapy (PDT); Uptake and Subcellular Localization of Photosensitizers; Mechanisms of PDT-Mediated Cytotoxicity; Direct Effects; Indirect Effects; Cytoprotective Mechanisms:; Importance of the Tumor Microenvironment in PDT; Role of Nitric Oxide in PDT; PDT and the Immune System; Delivery and Selectivity of PS; Clinical Indications for PDT; References; Part II; Mechanistic Aspects Involved in Resistance to PDT; Chapter-2 Changes in Cytoskeleton, Cell to Cell Adhesion and Adhesion to Substrate in PDT Resistant CellsNitric Oxide; Hypoxia; Conclusions and Future Directions; References; Chapter-3; Tumor Microenvironment as a Determinant of Photodynamic Therapy Resistance; Introduction; The Hypoxia Story; Fluence Rate Effects; Fractionated Illumination; New Light Sources; A Role for Tumor Stroma; Vascular Basement Membrane; Interstitial Stroma; Cell-Matrix and Cell-Cell Associations; Mitigating the Molecular Microenvironment; Cell Signaling; Stress Response; Angiogenic Factors; Transport Proteins The Importance of Combination Therapy to Overcoming Treatment ResistanceMicroenvironmental Monitoring; Techniques for Measuring Oxygenation and Blood Flow; Techniques for Measuring Photosensitizer Levels and Photobleaching; Conclusions; References; Chapter-4; Autophagy Induced by Photodynamic Therapy (PDT): Shaping Resistance Against Cell Death and Anti-Tumour Immunity; Introduction; Autophagy Pathways in Cancer Progression and Therapy Response: State-of-the-Art and Emerging Trends; Autophagy Pathways and PDT-Induced Cancer Cell Death: The Ying and the Yang Mechanisms of Resistance to Photodynamic Therapy: An UpdateIntroduction; Photosensitizer Uptake and Efflux in Resistant Cells; The Role of P-glycoprotein in the Efflux of PS; Reversal of MDR by PDT; ABCG2-mediated Efflux of PS and Its Role in Cross Resistance; Apoptosis and Resistance to PDT and its Relationship with PS Structure; Activation of Caspases and Expression of Apoptotic and Anti-apoptotic Proteins in PDT Resistant Cells; Cellular Antioxidant Defense Mechanisms; Heat Shock Proteins in the Response to Photodamage