Liquid Biopsy: New Challenges in the era of Immunotherapy and Precision Oncology

Front Cover
Liquid Biopsy
Copyright Page
Contents
List of contributors
Preface
1 What is precision medicine in oncology?
	1.1 Introduction: what does precision medicine mean?
	1.2 The role of biomarkers in precision medicine
	1.3 Classification of biomarkers
	1.4 The rationale for the definition of tumor mutational burden
	1.5 Collecting samples for mutational analysis: tissue or liquid biopsy?
	1.6 Pragmatical aspects of precision medicine: how to build it?
	1.7 Precision medicine and clinical trials: is there something different?
	1.8 Precision medicine in oncology: what is its “area-of-application”?
	1.9 Pharmacogenomics and precision medicine
	1.10 Determination of programmed death-ligand 1 expression in non-small cell lung carcinoma in order to choose patients eli...
	1.11 Through the concept of synthetic lethality: poly ADP-ribose polymerases-inhibitors and precision medicine
	1.12 Colorectal cancer e microsatellite instability
	1.13 Conclusions
	Conflict of interest statement
	References
2 Liquid biopsy: a right tool in a right context?
	Subchapter 2.1 Liquid biopsy in NSCLC
		Learning objectives
		2.1.1 Expert opinion
		2.1.2 Key points
		2.1.3 Summary of clinical recommendations
		Acknowledgments
		References
		Further reading
	Subchapter 2.2 The role of mutated ctDNA in nonmalignant lesions: challenging aspects in liquid biopsy implementation
		Learning objectives
		2.2.1 Expert opinion
		2.2.2 Key points
		Acknowledgments
		References
		Further reading
3 Liquid biopsy: new challenges in the era of immunotherapy and precision oncology NGS and the other faces of molecular biology
	Learning objectives
	3.1 Tissue or liquid biopsy?
	3.2 Next-generation sequencing for identification of gene alterations in liquid biopsy
	3.3 Liquid biopsy in monitoring response to therapy
	3.4 Expert opinion
	3.5 Key points
	3.6 Hints for deeper insight
	References
	Further reading
4 Current clinically validated applications of liquid biopsy
	Learning objectives
	4.1 Circulating tumor DNA in advanced non-small cell lung cancer
		4.1.1 Treatment-naïve advanced non-small cell lung cancer patients
		4.1.2 Advanced non-small cell lung cancer patients progressing during tyrosine kinase inhibitors
	4.2 Emerging clinical applications of liquid biopsy
		4.2.1 Colorectal cancer
		4.2.2 Breast cancer
		4.2.3 Melanoma
	4.3 Liquid biopsy application in clinical research
		4.3.1 Monitoring of treatment response in lung cancer
		4.3.2 Monitoring of treatment response in colorectal cancer
	4.4 Key points
	Acknowledgments
	References
5 Liquid biopsy and immunotherapy: is all that glitter gold?
	Learning objectives
	5.1 Background: the need for predictive biomarkers for patient selection
		5.1.1 Circulating tumor cells, cell-free DNA, and exosomes
		5.1.2 Circulating tumor cells
		5.1.3 Cell-free DNA and circulating tumor DNA
		5.1.4 Exosomes
		5.1.5 T-lymphocytes (the T-cell receptor) and cytokines
		5.1.6 The soluble form of immune-checkpoints and other circulating proteins
	Abbreviations
	Key points
	Expert opinion
	Acknowledgments
	References
6 Which technology performs better? From sample volume to extraction and molecular profiling
	Subchapter 6.1 Molecular profiling
		Learning objectives
		6.1.1 Expert opinion
		6.1.2 Key points
		References
		Further reading
	Subchapter 6.2 Biological fluid withdrawal: how much sample volume is enough?
		Learning objectives
		6.2.1 Introduction
		6.2.2 Other body fluids used in liquid biopsy-based assays
		6.2.3 Key points
		References
		Further reading
	Subchapter 6.3 Methods for cf/ct DNA isolation
		Learning objectives
		6.3.1 Key points
		Acknowledgments
		References
		Further reading
	Subchapter 6.4 CTC and exosome: from the enrichment to the characterization
		Learning objectives
		6.4.1 Introduction
		6.4.2 Exosome enrichment
		6.4.3 Exosomes characterization
			6.4.3.1 Role of exosomes in immunotherapy
		6.4.4 Circulating tumor cells enrichment methods
			6.4.4.1 Role of circulating tumor cells in immunotherapy
		6.4.5 Key points
		References
		Further reading
	Subchapter 6.5 Circulating RNAs (miRNA, lncRNA, etc): from the enrichment to the characterization
		Learning objectives
		6.5.1 Introduction
		6.5.2 Housekeeping RNAs
		6.5.3 Regulatory ncRNAs
		6.5.4 Key points
		6.5.5 Expert opinion
		Acknowledgments
		References
		Further reading
	Subchapter 6.6 Cell-free/circulating tumor DNA profiling: from next-generation sequencing-based to digital polymerase chain...
		Learning objectives
		6.6.1 Introduction
		6.6.2 Targeted next-generation sequencing methods
		6.6.3 Untargeted next-generation sequencing methods
		6.6.4 Droplet digital polymerase chain reaction methods
		6.6.5 Key points
		6.6.6 Expert opinion
		Acknowledgments
		References
	Subchapter 6.7 Standardization and quality assurance in liquid biopsy testing
		Learning objectives
		6.7.1 Introduction
		6.7.2 Cell-free DNA in liquid biopsy: preanalytical limitations
		6.7.3 The preanalytical phase of circulating tumor cells analysis
		6.7.4 The preanalytical phase of exosomes analysis
			6.7.4.1 Sample collection, storage, and processing
			6.7.4.2 Exosomes isolation
				6.7.4.2.1 Ultracentrifugation-based isolation techniques
				6.7.4.2.2 Ultrafiltration and size exclusion chromatography
				6.7.4.2.3 Polymer precipitation
				6.7.4.2.4 Immunoaffinity methods
				6.7.4.2.5 Microfluidics-based methods
		6.7.5 Standardization initiatives and ISO/CEN/external quality assessment development in liquid biopsy
		6.7.6 Key points
		6.7.7 Expert opinion
		Acknowledgments
		References
		Further reading
7 Early detection screening: myth or reality?
	References
8 Molecular tumor board
	Learning objectives
	Expert opinion
	Key points
	Acknowledgments
	References
9 Future perspectives
	Acknowledgments
	References
Glossary
Index
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