Predictive Drug Testing on Human Tumor Cells


Book Description

Predictive drug testing on human tumor cells in order to define the appropriate chemotherapy will remain imperative as long as the anticancer agents available are few in number and show only limited activity. The advantages of an effective test would lie in obviating the need for testing antineoplastic agents on large cohorts of patients for assessment of drug activity (phase II studies) and in allowing determination of optimal use of anticancer agents (phase III trials). Such an in vitro test could help to better define dose and schedule of drugs preclinically. The additive value of individual drugs could be determined on tumor cells in vitro in order to define the best combination chemotherapy in vivo. Test-directed therapy would avoid unnecessary drug-related morbidity in patients with refractory tumors. Chemotherapy treatment would be more than justified even with side effects if palliation or even prolonged survival could be anticipated as a result. The benefits of predictive drug testing on human tumor cells would extend beyond improvement of individual patient treatment if the testing helped to identify new active agents. This spectrum of benefits to the entire field of oncology pro vides tremendous motivation for the development of such testing. Although a number of chemosensitivity tests have been proposed since the advent of modern anticancer chemotherapy, interest has been renewed by the possibility of cloning human tumor cells on agar plates, with a view to testing drug activity on cells with high pro liferation capacity.




Tumor Organoids


Book Description

Cancer cell biology research in general, and anti-cancer drug development specifically, still relies on standard cell culture techniques that place the cells in an unnatural environment. As a consequence, growing tumor cells in plastic dishes places a selective pressure that substantially alters their original molecular and phenotypic properties.The emerging field of regenerative medicine has developed bioengineered tissue platforms that can better mimic the structure and cellular heterogeneity of in vivo tissue, and are suitable for tumor bioengineering research. Microengineering technologies have resulted in advanced methods for creating and culturing 3-D human tissue. By encapsulating the respective cell type or combining several cell types to form tissues, these model organs can be viable for longer periods of time and are cultured to develop functional properties similar to native tissues. This approach recapitulates the dynamic role of cell–cell, cell–ECM, and mechanical interactions inside the tumor. Further incorporation of cells representative of the tumor stroma, such as endothelial cells (EC) and tumor fibroblasts, can mimic the in vivo tumor microenvironment. Collectively, bioengineered tumors create an important resource for the in vitro study of tumor growth in 3D including tumor biomechanics and the effects of anti-cancer drugs on 3D tumor tissue. These technologies have the potential to overcome current limitations to genetic and histological tumor classification and development of personalized therapies.




Anticancer Drug Development Guide


Book Description

This unique volume traces the critically important pathway by which a "molecule" becomes an "anticancer agent. " The recognition following World War I that the administration of toxic chemicals such as nitrogen mustards in a controlled manner could shrink malignant tumor masses for relatively substantial periods of time gave great impetus to the search for molecules that would be lethal to specific cancer cells. Weare still actively engaged in that search today. The question is how to discover these "anticancer" molecules. Anticancer Drug Development Guide: Preclinical Screening, Clinical Trials, and Approval, Second Edition describes the evolution to the present of preclinical screening methods. The National Cancer Institute's high-throughput, in vitro disease-specific screen with 60 or more human tumor cell lines is used to search for molecules with novel mechanisms of action or activity against specific phenotypes. The Human Tumor Colony-Forming Assay (HTCA) uses fresh tumor biopsies as sources of cells that more nearly resemble the human disease. There is no doubt that the greatest successes of traditional chemotherapy have been in the leukemias and lymphomas. Since the earliest widely used in vivo drug screening models were the murine L 1210 and P388 leukemias, the community came to assume that these murine tumor models were appropriate to the discovery of "antileukemia" agents, but that other tumor models would be needed to discover drugs active against solid tumors.




Chemosensitivity


Book Description

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.







Chemosensitivity Testing in Oncology


Book Description

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.




Predictive Drug Testing on Human Tumor Cells


Book Description

Predictive drug testing on human tumor cells in order to define the appropriate chemotherapy will remain imperative as long as the anticancer agents available are few in number and show only limited activity. The advantages of an effective test would lie in obviating the need for testing antineoplastic agents on large cohorts of patients for assessment of drug activity (phase II studies) and in allowing determination of optimal use of anticancer agents (phase III trials). Such an in vitro test could help to better define dose and schedule of drugs preclinically. The additive value of individual drugs could be determined on tumor cells in vitro in order to define the best combination chemotherapy in vivo. Test-directed therapy would avoid unnecessary drug-related morbidity in patients with refractory tumors. Chemotherapy treatment would be more than justified even with side effects if palliation or even prolonged survival could be anticipated as a result. The benefits of predictive drug testing on human tumor cells would extend beyond improvement of individual patient treatment if the testing helped to identify new active agents. This spectrum of benefits to the entire field of oncology pro vides tremendous motivation for the development of such testing. Although a number of chemosensitivity tests have been proposed since the advent of modern anticancer chemotherapy, interest has been renewed by the possibility of cloning human tumor cells on agar plates, with a view to testing drug activity on cells with high pro liferation capacity.




Predictive Approaches in Drug Discovery and Development


Book Description

Practical Utility of Biomarkers in Drug Discovery and Development covers all aspects of biomarker research applied to drug discovery and development and contains state-of-the-art appraisals on the practical utility of genomic, biochemical, and protein biomarkers. Case histories and lessons from successful and unsuccessful applications of biomarkers are included along with key chapters on GLP validation, safety biomarkers and proteomics biomarkers. Regulatory agency perspectives and initiatives both in the US and internationally are also discussed.




Molecular Targeted Radiosensitizers


Book Description

Molecular Targeted Radiosensitizers: Opportunities and Challenges provides the reader with a comprehensive review of key pre-clinical research components required to identify effective radiosensitizing drugs. The book features discussions on the mechanisms and markers of clinical radioresistance, pre-clinical screening of targeted radiosensitizers, 3D radiation biology for studying radiosensitizers, in vivo determinations of local tumor control, genetically engineered mouse models for studying radiosensitizers, targeting the DNA damage response for radiosensitization, targeting tumor metabolism to overcome radioresistance, radiosensitizers in the era of immuno-oncology, and more. Additionally, the book features discussions on high-throughput drug screening, predictive biomarkers, pre-clinical tumor models, and the influence of the tumor microenvironment and the immune system, with a specific focus on the challenges radiation oncologists and medical oncologists currently face in testing radiosensitizers in human cancers. Edited by two acclaimed experts in radiation biology and radiosensitizers, with thirteen chapters contributed by experts, this new volume presents an in-depth look at current developments within a rapidly moving field, with a look at where the field will be heading and providing comprehensive insight into the framework of targeted radiosensitzer development. Essential reading for investigators in cancer research and radiation biology.




Precision Medicine in Oncology


Book Description

A FRESH EXAMINATION OF PRECISION MEDICINE'S INCREASINGLY PROMINENT ROLE IN THE FIELD OF ONCOLOGY Precision medicine takes into account each patient's specific characteristics and requirements to arrive at treatment plans that are optimized towards the best possible outcome. As the field of oncology continues to advance, this tailored approach is becoming more and more prevalent, channelling data on genomics, proteomics, metabolomics and other areas into new and innovative methods of practice. Precision Medicine in Oncology draws together the essential research driving the field forward, providing oncology clinicians and trainees alike with an illuminating overview of the technology and thinking behind the breakthroughs currently being made. Topics covered include: Biologically-guided radiation therapy Informatics for precision medicine Molecular imaging Biomarkers for treatment assessment Big data Nanoplatforms Casting a spotlight on this emerging knowledge base and its impact upon the management of tumors, Precision Medicine in Oncology opens up new possibilities and ways of working – not only for oncologists, but also for molecular biologists, radiologists, medical geneticists, and others.