[PDF] Resistance To Targeted Therapies In Multiple Myeloma eBook

Author : Silvia CW Ling
Publisher : Springer Nature
Page : 154 pages
File Size : 45,63 MB
Release : 2021-07-23
Category : Medical
ISBN : 3030734404

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Multiple Myeloma remains an incurable malignancy. As the disease progresses, it invariably becomes resistant to treatment and almost all patients develop refractory disease. There are multiple different types of targeted therapies and many of them are used in combination at different stages of disease. Targeted therapies that are approved to be used include Proteasome Inhibitors, Immunomodulatory Drugs and Monoclonal Antibodies. Second and third generations of these drugs are developed to overcome resistance and they have unique mechanism of actions. Targeted therapies that are undergoing clinical trials include CAR-T cells, bi-specific antibodies, vaccines, ubiquitin ligase inhibitors and BCL-2 inhibitors. This book will help to develop an understanding of targeted therapies in Multiple Myeloma. Its goal is to provide a unique review of the mechanism of action and resistance of the many targeted therapies in Multiple Myeloma by leaders of the field. The book will be useful for students in medical science, clinicians, health professionals, scientists, pharmaceutical professionals, drug developers, and policy makers. This book will provide an insightful knowledge of the biology of Multiple Myeloma, the mechanism of action and resistance of targeted therapies, application of biomarkers and genomics and possible strategies in overcoming resistance and future development.

Author : Nikhil C. Munshi
Publisher : Springer Science & Business Media
Page : 291 pages
File Size : 21,10 MB
Release : 2012-12-09
Category : Medical
ISBN : 1461452600

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Despite the advances in conventional, novel agent and high dose chemotherapy multiple myeloma (MM) remains incurable. In order to overcome resistance to current therapies and improve patient outcome, novel biologically-based treatment approaches are being developed. Current translational research in MM focusing on the development of molecularly-based combination therapies has great promise to achieve high frequency and durable responses in the majority of patients. Two major advances are making this goal possible. First, recent advances in genomics and proteomics in MM have allowed for increased understanding of disease pathogenesis, identified novel therapeutic targets, allowed for molecular classification, and provided the scientific rationale for combining targeted therapies to increase tumor cell cytotoxicity and abrogate drug resistance. Second, there is now an increased understanding of how adhesion of MM cells in bone marrow (BM) further impacts gene expression in MM cells, as well as in BM stromal cells (BMSCs). As a result of these advances in oncogenomics on the one hand and increased understanding of the role of the BM in the pathogenesis of MM on the other, a new treatment paradigm targeting the tumor cell and its BM microenvironment to overcome drug resistance and improve patient outcome has now been developed. Thalidomide, lenalidomide, and Bortezomib are three agents which target the tumor cell in its microenvironment in both laboratory and animal models and which have rapidly translated from the bench to the bedside. Ongoing efforts are using oncogenomics and cell signaling studies to identify next generation of therapies in MM on the one hand, and to inform the design of combination trials on the other. This new paradigm for overcoming drug resistance and improving patient outcome in MM has great promise not only to change the natural history of MM, but also to serve as a model for targeted therapeutics directed to improve outcome of patients with MM.

Author : Nikhil C. Munshi
Publisher : Springer Science & Business Media
Page : 322 pages
File Size : 26,52 MB
Release : 2012-11-15
Category : Medical
ISBN : 146144666X

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Despite the advances in conventional, novel agent and high dose chemotherapy multiple myeloma (MM) remains incurable. In order to overcome resistance to current therapies and improve patient outcome, novel biologically-based treatment approaches are being developed. Current translational research in MM focusing on the development of molecularly-based combination therapies has great promise to achieve high frequency and durable responses in the majority of patients. Two major advances are making this goal possible. First, recent advances in genomics and proteomics in MM have allowed for increased understanding of disease pathogenesis, identified novel therapeutic targets, allowed for molecular classification, and provided the scientific rationale for combining targeted therapies to increase tumor cell cytotoxicity and abrogate drug resistance. Second, there is now an increased understanding of how adhesion of MM cells in bone marrow (BM) further impacts gene expression in MM cells, as well as in BM stromal cells (BMSCs). As a result of these advances in oncogenomics on the one hand and increased understanding of the role of the BM in the pathogenesis of MM on the other, a new treatment paradigm targeting the tumor cell and its BM microenvironment to overcome drug resistance and improve patient outcome has now been developed. Thalidomide, lenalidomide, and Bortezomib are three agents which target the tumor cell in its microenvironment in both laboratory and animal models and which have rapidly translated from the bench to the bedside. Ongoing efforts are using oncogenomics and cell signaling studies to identify next generation of therapies in MM on the one hand, and to inform the design of combination trials on the other. This new paradigm for overcoming drug resistance and improving patient outcome in MM has great promise not only to change the natural history of MM, but also to serve as a model for targeted therapeutics directed to improve outcome of patients with MM.

Author : Andrés J. M. Ferreri
Publisher : Springer
Page : 143 pages
File Size : 35,67 MB
Release : 2018-04-04
Category : Medical
ISBN : 3319751840

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In the last decade, the literature on molecular mechanisms and activated pathways in the different lymphoma categories increased exponentially, which was followed by a more diffuse and successful use of targeted therapies. In this book, expert authors revisit the most relevant aspects of these therapies, with special emphasis on molecular mechanisms and clinical effects of resistance. The knowledge of the underlying mechanisms involved in tumor resistance to target therapies is of paramount importance because they will result in a better selection of patients with sensitive disease and the establishment of suitable combinations of drugs that target different molecules and could overcome the established resistance.

Author : Kenneth C. Anderson
Publisher : Informa Medical
Page : 320 pages
File Size : 36,79 MB
Release : 2007-12-01
Category : Medical
ISBN : 9781439818190

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Although treatable with conventional and high dose therapies, multiple myeloma (MM) remains incurable. However, recent advances in oncogenomics, coupled with increased understanding of the role of the bone marrow (BM) microenvironment in MM pathogenesis, has provided the basis for a new treatment paradigm targeting the tumor cell in the BM milieu to overcome conventional drug resistance and improve patient outcome. This text will first describe advances in molecular pathogenesis of MM due to cutting edge comparative genomic hybridization, gene microarray, and proteomic profiling of MM cells. The molecular basis for the growth, survival, drug resistance, and migration of MM cells, including extracellular matrix proteins, BM stromal cells, and cytokines in the BM milieu, will next be delineated using both laboratory and animal model systems. Importantly, recent advances in the pathogenesis of bone disease in MM will be described. These preclinical studies all will set the stage for the bench to bedside translation of scientific advances to the clinic to improve patient outcome. The clinical approach to patients with plasma cell dyscrasias has been transformed in the past 5 years. There are now uniform definitions of monoclonal gammopathy of unclear significance and improved predictors of who will develop MM. Biologically-based prognostic factors form the basis for new staging systems predictive of patient outcome. The approach to the patient with newly diagnosed, relapsed, and relapsed refractory MM has been transformed, with improved overall and extent of response as well as progression-free and overall survival, in both transplant candidates and elderly patients. Novel targeted therapies and immune-based strategies hold great promise to enhance treatment options even further. Finally our ability to identify, prophylax, and treat complications of MM and its treatment has advanced in a parallel fashion. Myeloma therefore represents a novel treatment paradigm targeting the tumor cell, tumor host interaction, and tumor microenvironment which can serve as a model to outcome in patients with other hematologic cancers and solid tumors as well.

Author : Khalid Ahmed Al-Anazi
Publisher :
Page : 236 pages
File Size : 10,36 MB
Release : 2019-02
Category : Neoplasms. Tumors. Oncology. Including cancer and carcinogens
ISBN : 178985217X

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This book is a comprehensive overview of the recent developments in the clinical and research fields of multiple myeloma. It is divided into three main sections that cover a wide range of topics, including: epidemiology and pathogenesis of the disease, genetic targets and pathways, resistance to novel therapies, angiogenesis and anti-angiogenesis, hematopoietic stem cell transplantation, role of radiology and radiotherapy in myeloma, infectious complications, and management of multiple myeloma in resource-poor countries.

Author : Gerrard K H Teoh
Publisher : World Scientific
Page : 201 pages
File Size : 14,34 MB
Release : 2009-03-13
Category : Medical
ISBN : 9814469629

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This very provocative book takes the reader on a “think-out-of-the-box” journey through the development of a treatment regimen for multiple myeloma called “dtZ”. It is a firsthand account of how more than 50 patients with myeloma were given a non-toxic, precisely-targeted, anti-cancer treatment that was specifically adapted to their individual cancers. These Individualized Anti-Cancer Targeted Therapies (smart bombs) have produced amongst the best responses as well as survival rates for myeloma. Accordingly, the author argues that some patients might even have been “cured” of their cancers.The concepts and logic behind “dtZ” are carefully presented in simple language so that both doctors and patients can easily understand them. Numerous tables and figures are provided, together with clear and simple explanations. This book is a valuable resource for all patients with myeloma who want to get the most out of their treatment by individualizing treatment to suit their needs, particularly for patients who have just been diagnosed with myeloma and who are taking that very important first step in their treatment. It is also a useful guide for doctors, nurses and researchers who treat and/or study myeloma.

Author : Morie A. Gertz
Publisher : Springer Science & Business Media
Page : 311 pages
File Size : 38,8 MB
Release : 2013-10-01
Category : Medical
ISBN : 1461485207

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This is a comprehensive, state-of-the-art guide to the diagnosis, treatment, and biology of multiple myeloma and related plasma disorders. Edited and written by a multidisciplinary group of recognized authorities from the Mayo Clinic, it presents clear guidelines on diagnosis and therapy and covers all aspects of multiple myeloma, from molecular classification and diagnosis, to risk stratification and therapy. Closely related plasma cell disorders such as solitary plasmacytoma, Waldenstrom macroglobulinemia, and light chain amyloidosis are discussed in detail as well. The book addresses often overlooked topics, including the role of radiation therapy, vertebral augmentation, and supportive care. Our understanding of this group of disorders is developing at an unprecedented rate, and Multiple Myeloma meets the need among oncologists and hematologists for a clear, timely, and authoritative resource on their biology, diagnosis, and treatment.

Author : Kenneth C. Anderson
Publisher :
Page : 0 pages
File Size : 42,96 MB
Release : 2007
Category : Medical
ISBN : 9781416050827

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Although treatable with conventional and high dose therapies, multiple myeloma (MM) remains incurable. However, recent advances in oncogenomics, coupled with increased understanding of the role of the bone marrow (BM) microenvironment in MM pathogenesis, has provided the basis for a new treatment paradigm targeting the tumor cell in the BM milieu to overcome conventional drug resistance and improve patient outcome. This text will first describe advances in molecular pathogenesis of MM due to cutting edge comparative genomic hybridization, gene microarray, and proteomic profiling of MM cells. The molecular basis for the growth, survival, drug resistance, and migration of MM cells, including extracellular matrix proteins, BM stromal cells, and cytokines in the BM milieu, will next be delineated using both laboratory and animal model systems. Importantly, recent advances in the pathogenesis of bone disease in MM will be described. These preclinical studies all will set the stage for the bench to bedside translation of scientific advances to the clinic to improve patient outcome. The clinical approach to patients with plasma cell dyscrasias has been transformed in the past 5 years. There are now uniform definitions of monoclonal gammopathy of unclear significance and improved predictors of who will develop MM. Biologically-based prognostic factors form the basis for new staging systems predictive of patient outcome. The approach to the patient with newly diagnosed, relapsed, and relapsed refractory MM has been transformed, with improved overall and extent of response as well as progression-free and overall survival, in both transplant candidates and elderly patients. Novel targeted therapies and immune-based strategies hold great promise to enhance treatment options even further. Finally our ability to identify, prophylax, and treat complications of MM and its treatment has advanced in a parallel fashion. Myeloma therefore represents a novel treatment paradigm targeting the tumor cell, tumor host interaction, and tumor microenvironment which can serve as a model to outcome in patients with other hematologic cancers and solid tumors as well.

Author : Mario Mandalà
Publisher : Springer
Page : 297 pages
File Size : 15,94 MB
Release : 2019-01-10
Category : Medical
ISBN : 3030105075

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A major objective of this book is to reveal unprecedented opportunities to understand and overcome drug resistance through the clinical assessment of rational therapeutic drug combinations and the use of predictive and prognostic biomarkers to enable patient stratification and tailor treatments. It offers to the readers an updated overview on the possible reasons of failure of new and promising therapeutic opportunities.