In spite of the development of various anticancer drugs, the therapy of cancer has remained challenging for decades. The current therapy of cancer is overwhelmed because of the inability to deliver therapeutics to all regions of a tumor in effective therapeutic concentrations, intrinsic or acquired resistance to the treatment with currently available agents via genetic and epigenetic mechanisms, and toxicity. As a result, cancer therapy using conventional therapeutics and different types of treatment regimens using this therapeutics has not led to a convincing survival benefit of the patients. In this context, Macromolecular therapeutics offer several advantages over conventional low molecular therapeutics by various ways such as, enable the use of larger doses of these agents by limiting the toxicity, by enhanced permeability and retention into tumors, by tumor targeting using tumor-specific antibodies, by specific inhibition of oncogenes using anticancer oligonucleotides etc. Cancer treatment using this macromolecular therapeutics has considerably improved the survival benefit for patients. As a result, various macromolecular therapeutics are already commercialized or are under clinical development. Although we are far from a real magic bullet today, looking at the pace of research and current success in this field of macromolecular therapeutics, it appears that we are approaching a magic bullet for the efficient treatment of cancer. Thus, we believe that the subject of this book is very timely, and that the book will fill an unmet need in the market.

This book is unique and assembles various types and aspects of macromolecular anticancer therapeutics for cancer therapy in one shell and conveys the importance of this interdisciplinary field to the broad audience. Thus, in a nutshell, this book details the basics of cancer, and various therapeutic strategies such as those based on macromolecular therapeutics hence can become an important reference for practitioners, oncologists, medical pharmacologists, medicinal chemists, biomedical scientists, experimental pharmacologists, pharmaceutical technologists, and particularly it can essentially become a handbook of macromolecular therapeutics for cancer therapy for graduates, post-graduates and Ph.D. students in these fields.

Macromolecular anticancer therapeutics encompasses macromolecule-conjugated anticancer prodrugs or macromolecules themselves for the treatment of cancer Emphasizes various types and aspects of macromolecular anticancer therapeutics such as polymer-based anticancer therapeutics, antibody-directed anticancer therapeutics, lipid-based anticancer therapeutics and nucleic acid therapeutics (see table of contents) Various chapters in this book are to be written by pioneer scientists and experts in the respective fields Includes supplementary material: sn.pub/extras

Autorentext

L. Harivardhan Reddy is Head of Nanovectors group at Sanofi-aventis, France. He completed Ph.D. in Pharmaceutics and Drug delivery in 2005 from The M.S. University of Baroda, India. He has worked for 4 years in two popular pharmaceutical companies (Sun Pharmaceutical Industries Ltd., and Aristo Pharmaceuticals Ltd.) in India, on drug delivery applications. He worked for 3 years (2005-2008) with anticancer drug delivery specialist Prof. Patrick Couvreur in CNRS lab at Université Paris-Sud, Chatenay-Malabry, France. He is an inventor of 3 patents belonging to macromolecular therapeutics and drug delivery. He has published, as an author and co-author, more than 60 publications in various reputed journals. He is also a reviewer for more than 15 journals of the fields of biomacromolecules, drug delivery, cancer therapy, and pharmacology. He is a member of The European Association for Cancer Research. His principal research interests are supramolecular lipidic prodrug nanomedicines and nanotherapeutics for cancer.

Patrick Couvreur is a Full Professor of Pharmacy at the University Paris-Sud, France, and holder of the chair of "Innovation Technologique" (2009-2010) at the prestigious 'Collège de France'. He is a member of the Academy of Technologies (France), of the Academy of Pharmacy (France) and corresponding member of the Royal Academy of Medicine (Belgium). Prof. Patrick COUVREUR's contributions in the field of drug delivery and targeting are highly recognized and respected around the world. Patrick COUVREUR performed a pioneer work together with Peter SPEISER, and demonstrated for the first time in 1977 that nanoparticles may be used as intracellular carriers for compounds which don't diffuse spontaneously into cells. Patrick COUVREUR's research is primarily on polymer-based and metallic-based nanomedicines, surface engineered nanosystems, and also focuses on lipid-based nanocarriers. He has publishedas an author and co-author, 341 publications, 109 review articles and book chapters, 6 books as editor, 50 patents, and 193 invited and plenary lectures at national and international congresses. He has received Pharmaceutical Sciences World Congress Award (2004), the "Marie-Maurice Janot Lecture" (2008) and above all the prestigious "Host Madsen Medal" (2007) in honour of his outstanding research achievements. He is a Field Editor of "Pharmaceutical Research", European Editor of the "Journal of Nanoparticles Research", and is a reviewer of more than 15 high reputed journals in the fields of Drug delivery, cancer research, macromolecules, physical chemistry etc. He is acting or acted as Board of Governors of the Controlled Release Society (CRS), Board of APGI, Expert Member of the Board of Pharmaceutical Sciences, International Pharmaceutical Federation (FIP). His exceptional research has led to two start-up companies BIOALLIANCE and MEDSQUAL dealing with novel therapeutics, in France.

Inhalt
Chapter 1. Classification of anticancer drugs based on therapeutic targets Enrique Espinosa, César Gómez Raposo Section Contents Abstract 1 Introduction 2 Drugs directed against tumour dna 2.1 Drugs directly affecting DNA helix: alkylators 2.2 Inhibitors of DNA-related proteins 2.2.1 Topoisomerases inhibitors 2.2.2 Antimetabolites 2.2.3 Histone related enzymes 2.2.4 Inhibitors of transcription factors 2.3 Specific genes 3 Drugs directed against tumour RNA 4 Drugs directed against proteins in the tumour cell 4.1 Receptors in the tumour membrane 4.2 Intracellular pathways in tumour cells 4.3 Tubulin 5 Drugs acting on the endothelium 5.1 Inhibition of pro-angiogenic factors 5.2 Inhibition of vascular receptors 5.3 Inside the endothelium 6 Drugs directed against extracellular matrix 6.1 Matrix metalloproteinases inhibitors 6.2 Anti-integrin therapy 6.3 Copper chelators 6.4 L1-CAM protein 6.5 Thrombospondin and others 7 Immunotherapy 7.1 Antibody-based immunotherapy of cancer 7.1.1 Unconjugated monoclonal antibodies 7.1.2 Conjugated monoclonal antibodies 7.1.3 Monoclonal antibodies as immunogens 7.2 Cytokines in cancer immunotherapy 7.3 Cancer vaccines 7.3.1 Peptide vaccines 7.3.2 Dendritic cell-based cancer vaccines 7.3.3 Cellular vaccines 7.3.4 DNA vaccines 7.3.5 Heat shock protein vaccines 7.4 Adoptive TCell transfer for cancer immunotherapy 7.5 Natural killer cell-based immunotherapy 7.6 Regulatory cells and cancer immunotherapy 7.7 Toll-like receptors 8 Drugs acting on potentially metastatic sites and glands 9 Conclusion References Figure legends Tables Chapter 2. Signal transduction pathways as therapeutic targets in cancer therapy Michele Milella, Ludovica Ciuffreda, Emilio Bria Section Contents Abstract 1 Introduction 2 Protein tyrosine kinases (TK) as therapeutic targets 2.1 RTK as therapeutic targets: the paradigm of EGFR mutations in NSCLC 3 Cytoplasmic signaling intermediates 3.1 The Ras/Raf/MAPK pathway 3.2 The PI3K/AKT/mTOR pathway 3.3 Signaling crosstalk 4 Oncogenic addiction 4.1 Oncogenic shock 4.2 Oncogene amnesia 5 Open issues in the clinical development of signal transduction-targe…