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This book proposes the importance of new systems of drug design and delivery based on cancer pathophysiology in addition to cancer molecular and cellular biology. The current studies based on molecular and cellular biology while ignoring pathophysiology and pharmacology may be leading the development of antitumor drugs in the wrong direction and wasting a lot of money. Although there have been numerous reports of genetic and phenotypic changes in tumors, a large body of pathological and clinical evidence supports the conclusion that there are no pivotal changes in tumor cells that distinguish them consistently and reliably from normal dividing cells. Unlike using antibiotics against bacterial infection, therefore, anticancer agents (ACAs) need to be delivered selectively to tumor tissues and should be kept there long enough to reproduce the concentrations they reach in the Petri dish, which is a closed space where the cytocidal effects of any anticancer agents (ACAs) including molecular targeting agents are very strong. In the body, however, administered ACAs are cleared with the passage of time. Furthermore, most human cancers possess abundant stroma that hinders the penetration of drugs into the tumor microenvironment. Therefore, to overcome these difficulties, novel drug delivery systems have been designed, such as nanoparticles and ACA conjugated antibodies to stromal components and to cancer cell surface antigens. These advances are described in this book after the first section, which describes core features of the pathophysiology of the cancer microenvironment, on which these new developments are based.
List of contents
Preface.- Part I Cancer pathophysiology.- 1. The Cancer Stroma and its relevance to tumor survival.- 2. Cancer and blood coagulation .- 3. Tumor Blood Vessels as targets for cancer therapy.- 4. Stromal barriers within the tumor microenvironment and obstacles to nanomedicine.- Part II Antibody drug conjugates (ADC).- 1. Recent progress in linker technology for antibody-drug conjugates: Methods for connection and release.- 2. Preclinical studies of ADC therapy for solid tumors.- 3. ADCs on the market and in clinical development.- Part III Hybrid techniques of active and passive targeting.- 1. Micelles conjugated with a pilot molecule.- 2. Liposomes conjugated with a pilot molecule.- 3. Multifunctional Envelope-type Nano Devices (MEND) for cancer therapy.- Part IV Cancer stromal targeting (CAST) therapy and diagnosis.- 1. Principle of CAST.- 2. CAST therapy.- 3. CAST diagnosis.- Part V The Current Status of Cancer Drug Delivery Systems and Future Directions.- Index.
About the author
Yasuhiro Matsumura, MD, PhD, Director, Division of Developmental Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Japan
David Tarin, MD, PhD, FRCPath, Professor of Pathology, UC San Diego Moores Cancer Center, University of California, USA
Summary
This book proposes the importance of new systems of drug design and delivery based on cancer pathophysiology in addition to cancer molecular and cellular biology. The current studies based on molecular and cellular biology while ignoring pathophysiology and pharmacology may be leading the development of antitumor drugs in the wrong direction and wasting a lot of money. Although there have been numerous reports of genetic and phenotypic changes in tumors, a large body of pathological and clinical evidence supports the conclusion that there are no pivotal changes in tumor cells that distinguish them consistently and reliably from normal dividing cells. Unlike using antibiotics against bacterial infection, therefore, anticancer agents (ACAs) need to be delivered selectively to tumor tissues and should be kept there long enough to reproduce the concentrations they reach in the Petri dish, which is a closed space where the cytocidal effects of any anticancer agents (ACAs) including molecular targeting agents are very strong. In the body, however, administered ACAs are cleared with the passage of time. Furthermore, most human cancers possess abundant stroma that hinders the penetration of drugs into the tumor microenvironment. Therefore, to overcome these difficulties, novel drug delivery systems have been designed, such as nanoparticles and ACA conjugated antibodies to stromal components and to cancer cell surface antigens. These advances are described in this book after the first section, which describes core features of the pathophysiology of the cancer microenvironment, on which these new developments are based.
