Breast Cancer Chemosensitivity

In Breast Cancer Chemosensitivity, a group of world leading experts review critical aspects of resistance to systemic therapy in breast cancer patients. Beginning with a clinical overview of the problem, the book then focuses on the latest findings of molecular mechanisms of drug resistance. Coverage provides an example of using novel approaches for chemosensitization of breast cancer cells that gives readers an idea about the future direction in breast cancer treatment. It allows those who are interested in breast cancer therapy to get a jump-start on critical issues in breast cancer therapeutic resistance.

'It will form an important addition to a scientific library and a useful addition to the (contributions series) which should be part of any obstetrics and gynaecology library.' New Zealand Journal of Obstetrics and Gynaecology

Over the past 50 years many in vitro and in vivo drug response assay systems have been developed to determine the potential - tivity of chemotherapy agents. The idea was to eliminate ineffective agents and unnecessary toxic treatment while selecting drugs active in vitro or in the mouse model that might increase the probability of response in the patient. None of these test models, however, achieved routine clinical application in the past. This might be at least in part - lated to large discrepancies that were described between the s- cess rate of the assay systems and the clinical benefit in cancer - tients. The heterogeneity of chemosensitivity that exists between different tumors as well as between individual tumor lesions may be one explanation for these findings. Furthermore, different assay end points such as proliferation, metabolism, and vitality were - veloped to evaluate the effects of cytostatic drugs on tumor cells, and these might be related to the differing results. However, knowledge about procedures for assay-assisted treatment selection has increased rapidly within the past few years, and several studies suggest that test-directed chemotherapy selection now may - prove response rates and survival in various types of tumors. The International Society for Chemosensitivity Testing in - cology (ISCO) was founded to promote, coordinate, and improve clinical and laboratory research in the field of predictive drug te- ing in human tumor cells.

Internationally acclaimed integrative medical oncologist James W. Forsythe, M.D., H.M.D., has praised Diana Warren for courage and tenacity in her arduous battle against Stage II breast cancer. Doctor Forsythe insists that “Diana deserves kudos from people around the world, for refusing to subject her body to unnecessary standard chemo and radiation that unscrupulous allopathic oncologists kept trying to require her to endure.” Featured in many hot-selling books written by others including media personality Suzanne Somers, and also the author of many successful books himself, Doctor Forsythe has hailed Diana for her dogged determination amid a non-stop quest to find effective natural, non-toxic treatments as her health deteriorated, while also hunting for an experienced doctor licensed to avoid high-dose poisonous options. “I strongly recommend that everyone who suffers from cancer read Diana’s compelling tale,” Doctor Forsythe said. “Today, Diana is playing a formidable role in helping to lead the way as a true champion in a quest to inform the public of the urgent need to avoid toxic treatments when feasible in certain circumstances, and how to find acceptable natural remedies—plus the importance of avoiding ‘standard-of-care’ chemo and radiation when under the care and guidance of a qualified, licensed medical professional.” After reading many hundreds of books on cancer, Doctor Forsythe hails Diana’s publication as being “by far among the best from the viewpoint of a person who never attended medical school. Readers undoubtedly will benefit when learning of the exceptional example Diana has set for us all.”

A state-of-the art collection of readily reproducible laboratory methods for assessing chemosensitivity in vitro and in vivo, and for assessing the parameters that modulate chemosensitivity in individual tumors. Chemosensitivity, Volume 1: In Vitro Assays provides a panel of 16 in vitro measures of chemosensitivity in adherent and non-adherent cells for single agents and combinations of agents. In addition to immunohistochemical and imaging approaches, these assays include clonogenic, colorimetric, fluorometric, and physiological assays. Highlights include image analysis to assess drug sensitivity, high throughput approaches using green fluorescent protein, DIMSCAN (a microcomputer fluorescence-based assay), and the ChemoFx assay used in biotechnology. A companion volume, Volume 2: In Vivo Models, Imaging, and Molecular Regulators, provides protocols for classifying tumors into response categories and customizing chemotherapy regimens to individual patients.

A state-of-the art collection of readily reproducible laboratory methods for assessing chemosensitivity in vitro and in vivo, and for assessing the parameters that modulate chemosensitivity in individual tumors. Chemosensitivity,Volume 2: In Vivo Models, Imaging, and Molecular Regulators contains cutting-edge protocols for classifying tumors into response categories and for customizing therapy to individuals. These readily reproducible techniques allow measurements of DNA damage, apoptotic cell death, and the molecular and cellular regulators of cytotoxicity, as well as in vivo animal modeling of chemosensitivity. A companion volume, Volume 1: In Vitro Assays contains in vitro and in vivo techniques to identify which new agents or combination of agents are effective for each type of tumor.

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

Despite recent advances in adjuvant therapies of cancer, the regi mens of postoperative adjuvant chemotherapy treatment which are presently available fail to cure the majority of cancer patients. Pre operative (neoadjuvant) chemotherapy represents a new approach in drug scheduling, based on sound theoretical, pharmacokinetic, and experimental principles. The preoperative timing of chemotherapy before definitive sur gery is not a minor change in the therapy of cancer. To be successful, large numbers of practitioners and their patients must participate. Substantial alterations of many aspects of the present management of cancer will have to follow. Therefore, before such therapy can be fully and routinely implemented, results of the novel treatment and its rationale have to be carefully evaluated. In preoperative treatment, other features will likely gain impor tance. For the first time, clinicians have a chance to follow the in vivo response of the tumor exposed to preoperative chemotherapy. The subsequent histological assessment of the tumor sample may likely become an important prognostic guide, permitting more re fined individual approaches to the planning of postoperative adju vant treatment. The value of such a treatment strategy can already be appreciated in the clinical setting, as seen from the therapy of osteosarcoma. Furthermore, preoperative chemotherapy might render previously inoperable tumors operable and hence resectable with a curative intention. The preoperative reduction of tumor bulk may also effectively decrease the need for more radical operations, permitting a more uniform adoption of conservative surgery.