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Drug Targets in Cellular Processes of Cancer: From Nonclinical to Preclinical Models

Author: Hardeep Singh Tuli

Publisher: Springer Nature

Published: 2020-09-30

Total Pages: 228

ISBN-13: 981157586X

This book explores potential cellular drug targets for cancer therapy. The first couple of chapters describe conventional treatment (radiotherapy, chemotherapy, and immunotherapy) & detection (biosensors) strategies for cancer. In contrast, the subsequent chapters address the role of cyclin-dependent kinases and cell cycle regulatory proteins in the growth of cancer cells and their potential as target for cancer treatment. The book then discusses the regulation of various pro-apoptotic and anti-apoptotic proteins via chemotherapeutic drugs. In addition, it examines the molecular mechanisms that are critical for mediating autophagic cell death in cancer cells. It subsequently reviews the role of reactive oxygen (ROS) species during carcinogenesis and during chemotherapy, and the potential of anti-inflammatory routes for the development of new therapeutic modulators. Lastly, it describes therapeutic strategies that target the tumor microenvironment and various angiogenic pathways for the treatment of cancer and to develop personalized medicine. Given its scope, the book is valuable resource for oncologists, cancer researchers, clinicians, and pharmaceutical industry personnel.

Anticancer Drug Development Guide

Author: Beverly A. Teicher

Publisher: Springer Science & Business Media

Published: 2004-02-01

Total Pages: 514

ISBN-13: 1592597394

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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.

Tumor Organoids

Author: Shay Soker

Publisher: Humana Press

Published: 2017-10-20

Total Pages: 213

ISBN-13: 3319605119

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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.

Nanotherapeutics in Cancer

Author: Hardeep Singh Tuli

Publisher: CRC Press

Published: 2022-11-24

Total Pages: 279

ISBN-13: 100077662X

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The applications of nanoparticulate drug delivery have gained significant attention in cancer diagnosis and treatment. Owing to their unique features and design, nanomedicines have made remarkable progress in eliminating dreadful tumors. Research in cancer nanomedicine spans multitudes of drug-delivery systems that include high tumor-targeting ability, sensitivity toward tumor microenvironments, and improved efficacy. Various nanocarriers have been developed and approved for anti-tumor drug targeting. These nanocarriers, such as liposomes, micelles, nanotubes, dendrimers, and peptides, offer several advantages including high selectivity, multifunctionality, specificity, biocompatibility, and precise control of drug release. This book provides complete information about each aspect of nanomaterials and nanotherapeutics, including synthesis, analysis, disease diagnosis, mechanistic insight, targeted drug delivery, and clinical implications in a concise and informative way. It presents simple and reader-friendly representations of the mechanisms of action of nanomaterials on cellular targets and highlights the challenges in targeted drug delivery with ongoing chemotherapeutic drugs.

Improving and Accelerating Therapeutic Development for Nervous System Disorders

Author: Institute of Medicine

Publisher: National Academies Press

Published: 2014-02-06

Total Pages: 107

ISBN-13: 0309292492

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Improving and Accelerating Therapeutic Development for Nervous System Disorders is the summary of a workshop convened by the IOM Forum on Neuroscience and Nervous System Disorders to examine opportunities to accelerate early phases of drug development for nervous system drug discovery. Workshop participants discussed challenges in neuroscience research for enabling faster entry of potential treatments into first-in-human trials, explored how new and emerging tools and technologies may improve the efficiency of research, and considered mechanisms to facilitate a more effective and efficient development pipeline. There are several challenges to the current drug development pipeline for nervous system disorders. The fundamental etiology and pathophysiology of many nervous system disorders are unknown and the brain is inaccessible to study, making it difficult to develop accurate models. Patient heterogeneity is high, disease pathology can occur years to decades before becoming clinically apparent, and diagnostic and treatment biomarkers are lacking. In addition, the lack of validated targets, limitations related to the predictive validity of animal models - the extent to which the model predicts clinical efficacy - and regulatory barriers can also impede translation and drug development for nervous system disorders. Improving and Accelerating Therapeutic Development for Nervous System Disorders identifies avenues for moving directly from cellular models to human trials, minimizing the need for animal models to test efficacy, and discusses the potential benefits and risks of such an approach. This report is a timely discussion of opportunities to improve early drug development with a focus toward preclinical trials.

Preclinical Safety Evaluation of Biopharmaceuticals

Author: Joy A. Cavagnaro

Publisher: John Wiley & Sons

Published: 2013-03-07

Total Pages: 1012

ISBN-13: 1118679385

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"The goal is to provide a comprehensive reference book for the preclinicaldiscovery and development scientist whose responsibilities span target identification, lead candidate selection, pharmacokinetics, pharmacology, and toxicology, and for regulatory scientists whose responsibilities include the evaluation of novel therapies." —From the Afterword by Anthony D. Dayan Proper preclinical safety evaluation can improve the predictive value, lessen the time and cost of launching new biopharmaceuticals, and speed potentially lifesaving drugs to market. This guide covers topics ranging from lead candidate selection to establishing proof of concept and toxicity testing to the selection of the first human doses. With chapters contributed by experts in their specific areas, Preclinical Safety Evaluation of Biopharmaceuticals: A Science-Based Approach to Facilitating Clinical Trials: Includes an overview of biopharmaceuticals with information on regulation and methods of production Discusses the principles of ICH S6 and their implementation in the U.S., Europe, and Japan Covers current practices in preclinical development and includes a comparison of safety assessments for small molecules with those for biopharmaceuticals Addresses all aspects of the preclinical evaluation process, including: the selection of relevant species; safety/toxicity endpoints; specific considerations based upon class; and practical considerations in the design, implementation, and analysis of biopharmaceuticals Covers transitioning from preclinical development to clinical trials This is a hands-on, straightforward reference for professionals involved in preclinical drug development, including scientists, toxicologists, project managers, consultants, and regulatory personnel.

Antibody-Drug Conjugates

Author: Kenneth J. Olivier, Jr.

Publisher: John Wiley & Sons

Published: 2016-11-14

Total Pages: 560

ISBN-13: 111906080X

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Providing practical and proven solutions for antibody-drug conjugate (ADC) drug discovery success in oncology, this book helps readers improve the drug safety and therapeutic efficacy of ADCs to kill targeted tumor cells. • Discusses the basics, drug delivery strategies, pharmacology and toxicology, and regulatory approval strategies • Covers the conduct and design of oncology clinical trials and the use of ADCs for tumor imaging • Includes case studies of ADCs in oncology drug development • Features contributions from highly-regarded experts on the frontlines of ADC research and development

Targeted Cancer Therapy in Biomedical Engineering

Author: Rishabha Malviya

Publisher: Springer Nature

Published: 2023-04-11

Total Pages: 949

ISBN-13: 9811997861

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This book highlights the role of Biomedical Engineering (BME) used in diagnosis (e.g., body scanners) and treatment (radiation therapy and minimal access surgery in order to prevent various diseases). In recent years, an important progress has been made in the expansion of biomedical microdevices which has a major role in diagnosis and therapy of cancer. When fighting cancer, efficacy and speed are of the utmost importance. A recently developed microfluidic chip has enabled a breakthrough in testing the efficacy of specialized cancer drugs. Effective cancer-targeting therapies will require both passive and active targeting strategies and a thorough understanding of physiologic barriers to targeted drug delivery. Targeted cancer treatments in development and the new combinatorial approaches show promise for improving targeted anticancer drug delivery and improving treatment outcomes. This book discusses the advancements and innovations in the field of BME that improve the diagnosis and treatment of cancer. This book is focused on bioengineering approaches to improve targeted delivery for cancer therapeutics, which include particles, targeting moieties, and stimuli-responsive drug release mechanisms. This book is a useful resource for students, researchers, and professionals in BME and medicine.

Recent Advances in Cancer Diagnostics and Therapy

Author: Anjana Pandey

Publisher: CRC Press

Published: 2022-01-18

Total Pages: 233

ISBN-13: 1000528138

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This book provides information about different types and stages of cancer and their subtypes with their respective molecular mechanisms, etiology, histopathology, and cellular origins. This book also provides detailed information about cancer incidence, mortality, and different types of technologies both bio and nano employed in cancer diagnosis and screening, and their applications in cancer therapies. This book informs readers about molecular mechanisms of cancer, diagnosis, and therapies along with different computational techniques used on a single platform. The chapters include a broad and integrated perspective on cancer-related topics. This book covers both conventional and emerging techniques employed in cancer screening and diagnosis, including imaging, biomarker, and electrochemical nanosensor-based approaches with detailed information on sensor development. Similarly, this book also covers the mechanisms of different conventional and emerging herbal and nano therapies used in cancer treatment. The authors discuss applications of different computational and mathematical tools, such as machine-learning methods, that can be employed in cancer diagnosis and therapy at the level of personalized medicine. Features: Offers an integrated approach to provide information about all aspects of cancer biology, diagnosis, and therapy Focuses on both conventional and emerging tools/techniques applicable in cancer screening and diagnosis Covers the mechanisms of conventional and emerging anticancer drugs and therapies Provides insights about a personalized medicine-based approach in cancer diagnosis and therapy This book is essential for university students, course lecturers, researchers, and industrialists working in the fields of cancer biology, medicine, and pharmacology.

The Drug Development Paradigm in Oncology

Author: National Academies of Sciences, Engineering, and Medicine

Publisher: National Academies Press

Published: 2018-02-12

Total Pages: 145

ISBN-13: 0309457971

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Advances in cancer research have led to an improved understanding of the molecular mechanisms underpinning the development of cancer and how the immune system responds to cancer. This influx of research has led to an increasing number and variety of therapies in the drug development pipeline, including targeted therapies and associated biomarker tests that can select which patients are most likely to respond, and immunotherapies that harness the body's immune system to destroy cancer cells. Compared with standard chemotherapies, these new cancer therapies may demonstrate evidence of benefit and clearer distinctions between efficacy and toxicity at an earlier stage of development. However, there is a concern that the traditional processes for cancer drug development, evaluation, and regulatory approval could impede or delay the use of these promising cancer treatments in clinical practice. This has led to a number of effortsâ€"by patient advocates, the pharmaceutical industry, and the Food and Drug Administration (FDA)â€"to accelerate the review of promising new cancer therapies, especially for cancers that currently lack effective treatments. However, generating the necessary data to confirm safety and efficacy during expedited drug development programs can present a unique set of challenges and opportunities. To explore this new landscape in cancer drug development, the National Academies of Sciences, Engineering, and Medicine developed a workshop held in December 2016. This workshop convened cancer researchers, patient advocates, and representatives from industry, academia, and government to discuss challenges with traditional approaches to drug development, opportunities to improve the efficiency of drug development, and strategies to enhance the information available about a cancer therapy throughout its life cycle in order to improve its use in clinical practice. This publication summarizes the presentations and discussions from the workshop.