Sensitization Of Cancer Cells For Chemo Immuno Radio Therapy

This book reviews novel approaches developed to reverse tumor cell resistance to chemo/immuno/radio-therapy and the use of various sensitizing agents in combination with various cytotoxics. It also introduces several current approaches developed by established investigators that are aimed at overcoming resistance. This is the first volume to compile studies on tumor cell sensitization. It will prove useful for students, scientists, clinicians and pharmaceutical companies.

Current cancer therapies are focused on three general strategies: modifying intrinsic radiosensitivity via molecular targeting, manipulating microenvironmental factors to enhance tumor susceptibility to radiation, and improving delivery of radiation to critical tumor locations while sparing normal tissues. The goal of this volume is to describe a number of promising approaches corresponding to each strategy. In general, research in radiation oncology tends to be siloed into fundamental biology, physics or treatment delivery. The strategies for improving therapeutic ratio encompassed in this book will involve each of these components of radiation oncology. Thus, they will illustrate the variety of disparate approaches available for potentially improving the efficacy of radiotherapy, which may then stimulate discussion across disciplines and foster further translational investigations. Although a goal of each chapter will be to highlight advances within an approach, of equal importance will be the delineation of barriers to successful clinical application and how to overcome or minimize such impediments. Along these lines, because therapeutic ratio incorporates both tumor and normal tissue radio response, a point of emphasis will be the mechanistic rationale for selectively modifying tumor (sensitization) or normal cells (protection). Finally, whereas the literature is replete with studies describing potential targets/strategies for increasing the therapeutic ratio for radiotherapy, this book will focus on those supported by in vivo data consistent with impending translational application along with those that are already being evaluated in the clinic.

The history of the development of cancer therapy has been marked by a recurring pattern, one of initially exciting and encouraging results as new methods were introduced, followed by dismaying failures. The extremity of the disease and its high mortality have dictated that each means of damaging tumor cells would be rapidly explored and exploited as a mode of therapy, long before the correspond ing theory and technique were completely understood and perfected. Thus radiation was used as an antitumor agent almost immediately following recogni tion of its cytodestructive capability. Equally constant, following the rapid utilization of new therapeutic methods, has been a period of significant technical improvements. This second aspect of the pattern is also illustrated by the field of radiotherapy. New radiation sources, new methods of dosimetry, use of high-energy radiation, and other new techniques allowed the therapist to better focus upon the tumor and to improve the geometry of exposure. Thus, with each technical advance, the "reach" of radiotherapy was increased and damage to normal tissues was decreased. Inevitably, however, a limit was reached, a point at which clinicians and researchers realized they could go no further without returning to a more fundamental search, one based on the biology of the tumor cell itself.

Despite the significant advances in cancer therapy made through constant evaluation and analysis of treatment aftereffects, the disease still remains one of the foremost causes of mortality worldwide killing more than 12 million people annually. The prime reason behind the failure of conventional chemotherapeutics which are used as the chief regimen in the comprehensive treatment of cancers is the development of chemoresistance. It can be either intrinsic or acquired and is primarily mediated via different key regulators like MDR, MAPK, NF-κB, PI3K/Akt, Wnt signaling pathways etc. Thus, agents which can target these regulatory elements or pathways and in turn sensitize cancer cells to chemotherapy holds immense prospect. However, there is barely such comprehensive work available in scientific literature that explains how chemosensitization of cancer cells functions using different drug combinations and exhibit synergism. This book provides a detailed description of chemoresistance and chemosensitization, targets for chemosensitization and various approaches adapted in the process of chemosensitization. Furthermore, the book explicates the role of various chemosensitizers, both natural and synthetic in sensitizing cancer cells and also details the current research findings on chemosensitization of different cancer types in both pre-clinical and clinical settings. Contents: Introduction and Basic Concepts of Cancer (Devivasha Bordoloi, Bethsebie Lalduhsaki Sailo, Nafiseh Manteghi, Ganesan Padmavathi and Ajaikumar B Kunnumakkara ) Cancer Cell Chemoresistance: A Prime Obstacle in Cancer Therapy (Javadi Monisha, Aviral Jaiswal, Kishore Banik, Harsha Choudhary, Anuj Kumar Singh, Devivasha Bordoloi and Ajaikumar B Kunnumakkara) Bladder Cancer: Chemoresistance and Chemosensitization (Nand Kishor Roy, Anand Sharma, Anuj Kumar Singh, Devivasha Bordoloi, Bethsebie Lalduhsaki Sailo, Javadi Monisha and Ajaikumar B Kunnumakkara) Mechanism of Chemoresistance in Bone Cancer and Different Chemosensitization Approaches (Ganesan Padmavathi, Devivasha Bordoloi, Kishore Banik, Javadi Monisha, Anuj Kumar Singh and Ajaikumar B Kunnumakkara) Chemoresistance in Brain Cancer and Different Chemosensitization Approaches (Amrita Devi Khwairakpam, Javadi Monisha, Kishore Banik, Harsha Choudhary, Anand Sharma, Devivasha Bordoloi and Ajaikumar B Kunnumakkara) Phytochemicals as Chemosensitizers in Breast Cancer (Madhumita Roy, Ruma Sarkar, Apurba Mukherjee, Sutapa Mukherjee and Jaydip Biswas) Potential of Different Chemosensitizers to Overcome Chemoresistance in Cervical Cancer (Kishore Banik, Bethsebie Lalduhsaki Sailo, Krishan Kumar Thakur, Aviral Jaiswal, Javadi Monisha, Devivasha Bordoloi and Ajaikumar B. Kunnumakkara) Colon Cancer Chemoresistance and Chemosensitization (Muthu K Shanmugam, Arunasalam Dharmarajan, Frank Arfuso and Gautam Sethi) Cancer Cell Chemoresistance and Chemosensitization in Endometrial Cancer (Anuj Kumar Singh, Javadi Monisha, Kishore Banik, Harsha Choudhary, Amrita Devi Khwairakpam, Devivasha Bordoloi and Ajaikumar B Kunnumakkara) Different Approaches to Overcome Chemoresistance in Esophageal Cancer (Devivasha Bordoloi, Kishore Banik, Amrita Devi Khwairakpam, Anand Sharma, Javadi Monisha, Bethsebie Lalduhsaki Sailo and Ajaikumar B Kunnumakkara) Different Chemosensitization Approaches in Gastric Cancer (Harsha Choudhary, Devivasha Bordoloi, Jai Prakash, Nafiseh Manteghi, Ganesan Padmavathi, Javadi Monisha and Ajaikumar B Kunnumakkara) Chemoresistance and Chemosensitization in Hematological Malignancies (Ota Fuchs) Different Methods to Inhibit Chemoresistance in Hepatocellular Carcinoma (Anuj Kumar Singh, Nand Kishor Roy, Anand Anip, Kishore Banik, Javadi Monisha, Devivasha Bordoloi