Antiangiogenic Drugs as Chemosensitizers in Cancer Therapy

Description

Anti-angiogenic Drugs as Chemosensitizers in Cancer Therapy, Volume 19 focuses on the use of anti-angiogenic drugs as sensitizers of tumor cells to the inhibitory activity of antitumor agents. Conventional and novel anti-neoplastic agents (cytotoxic molecules, hormones/antihormones, immunotherapies) are taken into consideration, along with advances made in combination therapies. The book encompasses examples of studies on the use of antiangiogenic compounds―molecules that inhibit the growth of vessels inside a tumor―together with antineoplastic drugs in order to sensitize the resistant tumor to their cytotoxic effects, thus reducing adverse side reactions and resistance and improving the therapeutic response of cancer patients. In addition, the book discusses clinical applications in various types of cancer, such as colorectal, lung, breast, renal, genitourinary, skin and brain and circulating tumors. It is a valuable resource for cancer researchers, clinicians and members of the biomedical field who wants to be up-to-date on the most recent and promising developments in the field. Front Matter Copyright Dedication Cover Image Insert Contributors Preface About the Series Editor About the Volume Editor Aims and Scope for Series ``Cancer Sensitizing Agents for Chemotherapy´´ Aims and Scope of the Volume Introduction: How tumor-endothelial cell communication within the tumor microenvironment affects angiogenesis Introduction Tumor microenvironment components Biophysical determinants of TME for the control of angiogenesis Soluble proangiogenic factors VEGF PDGF FGF HGF/C-Met Inflammatory mediators Other regulatory systems Angiopoietins/Tie receptors Endothelin (ET) and endothelin receptors (ETR) Surface-associated modulators of angiogenesis Endogenous negative regulators of angiogenesis Heterogeneity of endothelial component as a modifier of antiangiogenic therapy Conclusions References Antiangiogenic drugs: Chemosensitizers for combination cancer therapy Introduction Antiangiogenic drugs Approved combinatorial regimens with antiangiogenic drugs Antiangiogenic drugs and chemotherapy Antiangiogenic drugs and hormonal therapy Antiangiogenic drugs and target therapies EGFR HER2 mTOR BRCA ALK MEK Antiangiogenic drugs and immune checkpoint inhibitors Conclusions Acknowledgment References Antiangiogenic agents in the treatment of colorectal, gastric, and gastroesophageal junction adenocarcinom Introduction Colorectal cancer Gastric cancer and gastroesophageal junction adenocarcinoma Ramucirumab Tyrosine kinase inhibitors (TKIs) Angiogenesis and immune checkpoint inhibitors (ICIs) Conclusions References Antiangiogenic drugs as chemosensitizer in renal cell cancer Introduction Clinical applications in renal cell cancer Conclusions References Antiangiogenic drugs as chemosensitizer in genitourinary cancer Introduction Urothelial cancer Testicular germ cell tumor Prostate cancer Conclusions References Antiangiogenic drugs as chemosensitizer in melanoma Introduction Insights concerning the molecular mechanisms of angiogenesis Vascular endothelial growth factor (VEGF) Angiopoietin-2 (ANG-2) Toll-like receptors (TLRs) Immune cells in microenvironment and angiogenesis Manipulation of angiogenesis by therapeutic agents in melanoma Evidence from clinical trials and possible perspectives Conclusion References Antiangiogenic drugs as chemosensitizers in hematological tumors Introduction The cross-talk between EPCs and other players in tumor angiogenesis enlights effective drug targets The antiangiogenic drugs in hematological malignancies Concluding remarks Acknowledgments References Metronomic chemotherapy and antiangiogenic drugs: Preclinical and clinical data Introduction Definition and multiple mechanisms of metronomic chemotherapy Recent clinical data from randomized phase II-III clinical trials involving metronomic chemotherapy Antiangiogenic activity of metronomic chemotherapy in preclinical and clinical setting Combinations of metronomic chemotherapy with antiangiogenic drugs Preclinical studies on the combination of metronomic chemotherapy and antiangiogenic drugs Preclinical studies with anti-VEGFR-2 antibody DC101 Preclinical studies with VEGFR-2 tyrosine kinase inhibitors Pazopanib Sorafenib Evaluation of other antiangiogenic tyrosine-kinase inhibitors Clinical studies on the combination of metronomic chemotherapy and antiangiogenic drugs Clinical trials with bevacizumab Clinical trials with tyrosine kinase inhibitors Conclusions References Resistance to antiangiogenic treatments: A review Introduction Basic concepts in angiogenesis and antiangiogenesis Antiangiogenic treatments and classes of resistance mechanisms Resistance to antiangiogenic treatments Causes of antiangiogenic treatment failure Causes of antiangiogenic treatment failure with low dose metronomic chemotherapy (MCT) Causes of treatment failure with antiangiogenic therapy Other angiogenic proteins Clinical approach to antiangiogenic resistance Discussion Intermittent antiangiogenic treatment Association of antiangiogenic drugs with immunological checkpoint inhibitors Conclusions Future perspectives References Predictive ``omic´´ biomarkers of drug response: Colorectal cancer as a model Introduction Somatic genomics EGFR-targeted therapy HER2-targeted therapy Tyrosine kinase-targeted therapy Microsatellite instability/mismatch repair-targeted therapy NTRK fusion-targeted therapy Germline pharmacogenetics/genomics Chemical drugs Biological drugs Transcriptomics Epigenomics DNA methylation and histone deacetylation Non-coding RNA MicroRNAs Long non-coding RNAs Proteomics Metabolomics Discussion and conclusions Acknowledgment References General conclusions and future perspectives General statements on tumor angiogenesis Strategies acting on hypoxic, acidic and oxidative environment Vascular normalizing strategies Control of lymphocyte trafficking into the TME Strategies acting on miRNA and epigenetic determinants Final considerations References Index A B C E G H I L M N P R S T U V