Biomarkers in Cancer Therapy : Liquid Biopsy Comes of Age

This book sheds new light on research into liquid biopsy biomarkers for cancer screening. The chapters in the first half address exosomes, circulating cell-free DNA and autoantibodies, and main solid cancers, along with companion biomarkers â#x80;#x93; all of which serve as the basis for exploring key research questions for future clinical trials in the bookâ#x80;#x99;s second half. The study of biomarkers has evolved rapidly thanks to advances in precision medicine. While conventional cancer biomarker research is focused on proteomics or gene analysis of resected tissue, diagnostic markers have since become significant in terms of gauging the effectiveness of molecularly targeted drugs or the likelihood of a favorable prognosis. In addition, conventional treatment strategy, which draws on archives of resected tissue samples, is now gradually being replaced by monitoring with the use of liquid biopsy, which is poised to become the new mainstream in molecular targeting therapy. The contributing authors discuss in detail biomarkers, molecular targets for treatment, monitoring markers to evaluate treatment responses, prognostic markers, and screening and early diagnosis. Accordingly, this excellent collection of texts will benefit not only oncologists, but also medical and biological researchers and pharmaceutical scientists involved in the latest cancer research Preface 5 Contents 6 Part I: Various Strategies to Detect Cancer 8 1: Liquid Biopsy Diagnostics Using Extracellular Vesicles 9 1.1 Introduction 10 1.2 General Remarks on EVs as Biomarkers 12 1.2.1 Molecular Characteristics of EVs 12 1.2.2 Purification and Detection Methods for EV Biomarkers 12 1.2.3 EV Protein Biomarkers and Liquid Biopsy for Cancer Diagnosis 13 1.3 Summary 13 References 14 2: Cell-Free DNA 17 2.1 Structure of cfDNA 18 2.2 Identification of the Origin of ctDNA 19 2.3 cfDNA as Mobile Genetic Elements 20 2.4 Cancer Genome Diversity and Cancer Clonal Evolution 21 2.5 ctDNA Assays in the Clinical Setting 21 2.5.1 ctDNA Assays for Cancer Treatment Selection 22 2.5.2 ctDNA Assays for Noninvasive Monitoring of Treatment Effects 22 2.5.3 ctDNA Assays for Detecting Residual Disease 23 2.5.4 ctDNA Assays for Cancer Screening in Asymptomatic Individuals 23 2.5.5 ctDNA Assays for Monitoring Tumor Dynamics 23 2.5.6 NGS-Based ctDNA Assays 25 2.6 False-Positive Plasma Genotyping Due to Clonal Hematopoiesis 25 2.7 Conclusion 25 References 25 3: Autoantibody in Cancer 31 3.1 Autoantibodies Are Sensitive and Stable Biomarkers 32 3.2 SEREX Method to Identify Autoantigens 32 3.3 Method to Examine Serum Antibody Levels 32 3.4 NY-ESO-1 Is Useful for Diagnosis and Therapeutic Treatment 34 3.5 p53 Antibody in Various Cancers 34 3.6 Autoantibodies in ESCC and CRC 34 3.7 Autoantibodies in Other Diseases 40 References 41 4: Serum Angiogenic Factors as Cancer Biomarkers 47 4.1 Introduction 47 4.2 Overexpression of Angiogenic Factors and Malignant Potential of Cancer 48 4.3 Overexpression of Angiogenic Factors and Treatment Response 49 4.4 Clinical Significance of Serum Levels of Angiogenic Factors 50 4.4.1 Serum VEGF 50 4.4.2 Serum Thymidine Phosphorylase (dThdPase) 51 4.4.3 Serum HGF 51 4.4.4 Serum Midkine 52 4.5 Conclusions 53 References 53 5: Biomarkers of Cancer Stem Cells in Cancer Therapy 56 5.1 Introduction 57 5.2 Treatment Targeting Surface Markers of CSCs 58 5.3 Treatments Based on Reprogramming Cancer Cells 60 5.4 Targeting Therapy with the Tumour Microenvironment 61 5.5 Conclusions 62 References 62 Part II: Biomarkers for Individual Cancers 65 6: Specifics 1: Head and Neck Cancer and Esophageal Cancer 66 6.1 Head and Neck Cancer 67 6.1.1 Introduction 67 6.1.2 Blood-Based Biomarkers (Liquid Biopsy) 67 6.1.2.1 Circulating Tumor DNA (ctDNA) 67 6.1.2.2 Circulating MicroRNAs (miRNAs) 68 6.2 Esophageal Cancer 68 6.2.1 Introduction 68 6.2.2 Tissue-Based Biomarkers 69 6.2.3 Blood-Based Biomarkers (Liquid Biopsy) 70 6.2.3.1 Circulating Tumor Cells (CTCs) 70 6.2.3.2 Cell-Free DNA (cfDNA) and Circulating Tumor DNA (ctDNA) 70 6.2.3.3 Circulating MicroRNAs (miRNAs) 71 6.2.3.4 Autoantibodies Against Tumor-Associated Antigens (TAAs) 71 Serum Anti-p53 Antibody 71 Other Autoantibodies 72 6.2.3.5 Serum Tumor Markers 72 6.2.3.6 Exosome 73 6.2.4 Biomarkers Using Breath and Headspace Vapor (Gas Analysis) 73 6.2.5 Future Directions 74 References 74 7: Biomarkers in Gastric Cancer 81 7.1 Introduction 82 7.2 Plasma/Serum Conventional Biomarkers for Gastric Cancers 82 7.3 Plasma/Serum RNA Biomarkers for Gastric Cancers 84 7.4 Peritoneal Solution Biomarkers of Gastric Cancers 85 7.5 Conclusion 86 References 87 8: Liquid Biopsy in Hepatocellular Carcinoma 89 8.1 Introduction 89 8.1.1 Circulating Tumor Cells 91 8.1.2 Circulating Tumor DNA 92 8.1.3 MicroRNAs 93 8.2 Perspective 94 References 95 9: Biomarkers of Pancreatic Cancer 98 9.1 Introduction 99 9.2 Circulating Tumor DNA (ctDNA) 99 9.3 Circulating Cell-Free RNA (cfRNA) 100 9.4 Approach for Detection of Precancer Lesion 101 9.5 Potential for Prognostic Marker 102 9.6 Conclusion 102 References 103 10: Biomarkers of Lung Cancer: Liquid Biopsy Comes of Age 106 10.1 Introduction 107 10.2 Materials of Liquid Biopsy 107 10.2.1 ctDNA 108 10.2.2 Real-Time qPCR 109 10.2.3 Digital PCR (dPCR) and BEAMing 109 10.2.4 Next-Generation Sequencing (NGS) 109 10.2.5 Circulating Tumor Cells (CTCs) 110 10.2.6 Clinical Application of CTCs 110 10.3 Liquid Biopsy for Companion Diagnosis 111 10.4 Future Direction of Liquid Biopsy 111 10.5 Conclusion 112 References 112 11: Biomarkers for Breast Cancer Treatment 115 11.1 Hormonal Receptors 116 11.1.1 The Research Background of Hormonal Receptors in Breast Cancer 116 11.1.2 The Structure of Hormonal Receptors 116 11.1.3 Hormonal Receptors as Biomarker for Breast Cancer Treatment 117 11.2 HER2 117 11.2.1 HER2 as Biomarker for Breast Cancer Treatment 117 11.3 Ki67 118 11.3.1 Ki67 as Biomarker for Breast Cancer Treatment 118 11.4 Oncotype DX 119 11.5 BRCA1/2 Mutation 120 11.6 Tumor Marker 120 References 121 12: Biomarkers of Prostate Cancer 125 12.1 Introduction 125 12.2 Serum Markers 126 12.2.1 PSA (Prostate-Specific Antigen) 126 12.2.2 proPSA 128 12.2.3 NSE (Neuron-Specific Enolase)/Chromogranin A/proGRP (Pro-Gastrin-Releasing Peptide) 128 12.2.4 Bone Turnover Markers 128 12.3 Urine Markers 129 12.3.1 PC3 (Prostate Cancer Gene 3) 129 12.4 Liquid Biopsy 129 12.4.1 CTC (Circulating Tumor Cells) 129 12.4.2 cfDNA (Cell-Free DNA)/ctDNA (Circulating Tumor DNA) 130 12.4.3 miRNA (MicroRNA) 130 References 130 13: Biomarkers of Gynecological Cancers 133 13.1 Ovarian, Fallopian Tube, and Peritoneal Cancers 134 13.1.1 Serum Biomarkers 134 13.1.1.1 CA125 134 Screening 134 Prognosis 137 Detecting Recurrence 138 13.1.1.2 Human Epididymis Protein 4 138 Screening 138 Differential Diagnosis 139 13.1.1.3 The Risk of Ovarian Malignancy Algorithm 139 13.1.1.4 Cell-Free DNA 139 13.1.1.5 DNA Methylation 139 13.1.1.6 Metabolites 140 13.1.1.7 MicroRNAs 140 13.1.1.8 Long Noncoding RNAs 140 13.1.1.9 Carcinoembryonic Antigen 141 13.1.1.10 Alpha-Fetoprotein 141 13.1.1.11 Inhibin 141 13.1.1.12 Cytokines 141 13.1.1.13 Other Markers 141 13.2 Uterine Cancers 142 13.2.1 CA125 142 13.2.2 HE4 142 13.2.3 Other Markers 143 13.3 Cervical Cancers 143 13.3.1 Squamous Cell Carcinoma Antigen 143 13.3.2 Serum Fragments of Cytokeratin 144 13.3.3 CA125 144 13.3.4 Other Markers 144 References 144 14: Biomarkers of Malignant Pleural Mesothelioma 151 14.1 Soluble Mesothelin-Related Peptides (SMRPs) 152 14.2 Megakaryocyte Potentiating Factor (MPF) 153 14.3 OPN 154 14.4 Fibulin-3 154 14.5 Other Biomarkers 155 14.5.1 Vascular Endothelial Growth Factor (VEGF) 155 14.5.2 High-Mobility Group Box 1 Protein (HMGB1) 155 14.5.3 Midkine 155 14.6 Conclusion 156 References 156 Front Matter ....Pages i-viii Front Matter ....Pages 1-1 Liquid Biopsy Diagnostics Using Extracellular Vesicles (Makoto Sumazaki, Koji Ueda)....Pages 3-10 Cell-Free DNA (Hiroyuki Yamamoto, Yoshiyuki Watanabe, Fumio Itoh)....Pages 11-24 Autoantibody in Cancer (Takaki Hiwasa, Hideaki Shimada)....Pages 25-40 Serum Angiogenic Factors as Cancer Biomarkers (Hideaki Shimada)....Pages 41-49 Biomarkers of Cancer Stem Cells in Cancer Therapy (Norikatsu Miyoshi, Tsunekazu Mizusima, Yuichiro Doki, Masaki Mori)....Pages 51-59 Front Matter ....Pages 61-61 Specifics 1: Head and Neck Cancer and Esophageal Cancer (Shuhei Ito, Kensuke Koike, Koshi Mimori)....Pages 63-77 Biomarkers in Gastric Cancer (K. Yamashita)....Pages 79-86 Liquid Biopsy in Hepatocellular Carcinoma (Eiichiro Suzuki, Tetsuhiro Chiba, Naoya Kato)....Pages 87-95 Biomarkers of Pancreatic Cancer (Takahiro Kishikawa, Minoru Tada, Motoyuki Otsuka, Kazuhiko Koike)....Pages 97-104 Biomarkers of Lung Cancer: Liquid Biopsy Comes of Age (Akihiko Miyanaga, Mari Masuda, Tesshi Yamada)....Pages 105-113 Biomarkers for Breast Cancer Treatment (Tetsu Hayashida, Yuko Kitagawa)....Pages 115-124 Biomarkers of Prostate Cancer (Koichiro Akakura)....Pages 125-132 Biomarkers of Gynecological Cancers (Tatsuyuki Chiyoda, Ai Dozen, Keiko Saotome, Yoshiko Nanki, Daisuke Aoki)....Pages 133-150 Biomarkers of Malignant Pleural Mesothelioma (Kazutoshi Isobe)....Pages 151-157 This book sheds new light on research into liquid biopsy biomarkers for cancer screening. The chapters in the first half address exosomes, circulating cell-free DNA and autoantibodies, and main solid cancers, along with companion biomarkers â#x80;#x93; all of which serve as the basis for exploring key research questions for future clinical trials in the bookâ#x80;#x99;s second half. The study of biomarkers has evolved rapidly thanks to advances in precision medicine. While conventional cancer biomarker research is focused on proteomics or gene analysis of resected tissue, diagnostic markers have since become significant in terms of gauging the effectiveness of molecularly targeted drugs or the likelihood of a favorable prognosis. In addition, conventional treatment strategy, which draws on archives of resected tissue samples, is now gradually being replaced by monitoring with the use of liquid biopsy, which is poised to become the new mainstream in molecular targeting therapy. The contributing authors discuss in detail biomarkers, molecular targets for treatment, monitoring markers to evaluate treatment responses, prognostic markers, and screening and early diagnosis. Accordingly, this excellent collection of texts will benefit not only oncologists, but also medical and biological researchers and pharmaceutical scientists involved in the latest cancer research