Principles of cancer genetics:
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| Main Author: | |
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| Format: | Book |
| Language: | English |
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Springer
[2022]
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| Edition: | Third edition |
| Subjects: | |
| Online Access: | Inhaltsverzeichnis Klappentext |
| Physical Description: | XIII, 431 Seiten Illustrationen |
| ISBN: | 9783030993894 |
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| 650 | 4 | |a Genetics | |
| 650 | 4 | |a Molecular Genetics | |
| 650 | 4 | |a Epigenetics | |
| 650 | 4 | |a Cancer Biology | |
| 650 | 4 | |a Cancer-Genetic aspects | |
| 650 | 4 | |a Genetics | |
| 650 | 4 | |a Molecular genetics | |
| 650 | 4 | |a Epigenetics | |
| 650 | 4 | |a Cancer | |
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Record in the Search Index
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| adam_text | ntents The Genetic Basis of Cancer.................................................................. The Cancer Gene Theory........................................................................... Cancers Are Invasive Tumors................................................................... Cancer Is a Unique Type of Genetic Disease........................................... What Are Cancer Genes and How Are They Acquired?......................... Mutations Alter the Human Genome........................................................ Genes and Mutations................................................................................. Single Nucleotide Substitutions.................................................................... Gene Silencing Is Marked by Cytosine Methylation: Epigenetics.......... Environmental Mutagens, Mutations, and Cancer....................................... Inflammation Promotes the Propagation of Cancer Genes....................... The Immune System Restrains Tumor Growth........................................ Stem Cells, Darwinian Selection, and the Clonal Evolution of Cancers................................................................................................... Selective Pressure and Adaptation: Hypoxia and Altered Metabolism................................................................................................. Multiple Somatic Mutations Punctuate ClonalEvolution......................... Tumor Growth Leads to Cellular Heterogeneity...................................... Tumors Are Distinguished by Their Spectrum of
Driver Gene Mutations and Passenger Gene Mutations...................................... Colorectal Cancer: A Model for Understanding the Step-Wise Process of Tumorigenesis.......................................................................... Do Cancer Cells Divide More Rapidly Than Normal Cells?................... Germline Cancer Genes Allow Neoplasia to Bypass Steps in Clonal Evolution.................................................................................................... Cancer Syndromes Reveal Rate-Limiting Steps in Tumorigenesis......... The Etiologic Triad: Heredity, the Environment, and Stem Cell Division...................................................................................................... Understanding Cancer Genetics................................................................ Further Reading.......................................................................................... 1 1 2 3 4 5 7 13 17 17 23 27 28 30 32 34 35 36 39 41 43 45 47 49 vii
viii 2 Contents Oncogenes............................................................................................................ What Is an Oncogene?................................................................................. The Discovery of Transmissible Cancer Genes......................................... Viral Oncogenes Are Derived from the Host Genome............................. The Search for Activated Oncogenes: The RAS Gene Family................ Complex Genomic Rearrangements: The MYC Gene Family................ Proto-oncogene Activation by Gene Amplification.................................. Proto-oncogenes Can Be Activated by Chromosomal Translocation ... Chromosomal Translocations in Liquid Tumors....................................... Chronic Myeloid Leukemia and the Philadelphia Chromosome............. Oncogenic Activation of Transcription Factors in Prostate Cancer and Ewing’s Sarcoma...................................................................... Oncogene Discovery in the Genomic Era: Mutations in PIK3CA........... Selection of Tumor-Associated Mutations................................................. Multiple Modes of Proto-oncogene Activation.......................................... Oncogenes Are Dominant Cancer Genes................................................... Germline Mutations in RET and MET Confer Cancer Predisposition... Proto-oncogene Activation and Tumorigenesis......................................... Further Reading........................................................................................... 3 Tumor
Suppressor Genes.............................................................................. What Is a Tumor Suppressor Gene?........................................................... The Discovery of Recessive Cancer Phenotypes....................................... Retinoblastoma and Knudson’s Two-Hit Hypothesis............................... Chromosomal Localization of the Retinoblastoma Locus........................ The Mapping and Cloning of the Retinoblastoma Gene.......................... Tumor Suppressor Gene Inactivation: The Second “Hit” and Loss of Heterozygosity......................................................................... Recessive Genes, Dominant Traits............................................................. APC Inactivation in Inherited and Sporadic Colorectal Cancers............. TP53 Is Frequently Inactivated During Tumorigenesis............................ Functional Inactivation of p53: Tumor Suppressor Genes and Oncogenes Interact................................................................................ Mutant TP53 in the Germline: Li Fraumeni Syndrome............................ Gains-of-Function Caused by Cancer-Associated Mutations in TP53......................................................................................................... Cancer Predisposition: Allelic Penetrance, Relative Risk and the Odds Ratio............................................................................................. Breast Cancer Susceptibility: BRCA 1 and BRCA2.................................... Genetic Losses on Chromosome 9:
CDKN2A........................................... Complexity at CDKN2A՛. Neighboring and Overlapping Genes.............. Genetic Losses on Chromosome 10: PTEN............................................... SMAD4 and the Maintenance of Stromal Architecture............................. Two Distinct Genes Cause Neurofibromatosis.......................................... Patched Proteins Regulate Developmental Morphogenesis...................... 51 51 51 54 57 60 61 63 64 65 69 71 73 74 75 76 77 79 81 81 81 83 86 87 90 92 93 96 98 Ю0 103 104 HO 113 116 118 121 124 126
ontents ix von Hippel-Lindau Disease........................................................................ NOTCHl: Tumor Suppressor Gene or Oncogene?.................................. Multiple Endocrine Neoplasia Type 1....................................................... Most Tumor Suppressor Genes Are Tissue-Specific................................ Modeling Cancer Syndromes in Mice....................................................... Genetic Variation and Germline Cancer Genes........................................ Tumor Suppressor Gene Inactivation During Colorectal Tumorigenesis............................................................................................. Inherited Tumor Suppressor Gene Mutations: Gatekeepers and Landscapers......................................................................................... Maintaining the Genome: Caretakers........................................................ Further Reading.......................................................................................... 128 128 129 130 131 134 Genetic Instability and Cancer............................................................... What Is Genetic Instability?....................................................................... The Majority of Cancer Cells Are Aneuploid........................................... Aneuploid Cancer Cells Exhibit Chromosome Instability....................... Chromosome testability Arises Early in Colorectal Tumorigenesis .... Chromosomal Instability Accelerates Clonal Evolution........................... Aneuploidy Can Result
from Mutations that Directly Impact Mitosis........................................................................................................ STAG2 and the Cohesion of Sister Chromatids........................................ Other Genetic and Epigenetic Causes of Aneuploidy.............................. Transition from Tetraploidy to Aneuploidy during Tumorigenesis.... Multiple Forms of Genetic testability in Cancer...................................... Defects in Mismatch Repair Cause Hereditary Nonpolyposis Colorectal Cancer....................................................................................... Mismatch Repair-Deficient Cancers Have a Distinct Spectrum of Mutations.................................................................................................... Defects in Nucleotide Excision Repair Cause Xeroderma Pigmentosum.............................................................................................. NER Syndromes: Clinical Heterogeneity and Pleiotropy........................ DNA Repair Defects and Mutagens Define Two Steps Towards Genetic testability...................................................................................... Defects in DNA Crosslink Repair Cause Fanconi Anemia...................... A Defect in DNA Double Strand Break Responses Causes Ataxia-Telangiectasia................................................................................. A Unique Form of Genetic testability Underlies Bloom Syndrome.... Aging and Cancer: Insights from the Progeroid Syndromes.................... Instability at the End:
Telomeres and Telomerase.................................... Overview: Genes and Genetic Stability.................................................... Further Reading.......................................................................................... 141 141 142 145 147 148 135 138 139 140 149 151 153 154 156 158 163 165 171 172 174 178 182 185 188 191 192
x 5 6 Contents Cancer Genomes......................................... Discovering the Genetic Basis of Cancer: From Genes to Genomes ... What Types of Genetic Alterations Are Found in Tumor Cells?............. How Many Genes Are Mutated in the Various Types of Cancer?........... What Is the Significance of the Mutations that Are Found in Cancers?....................... When Do Cancer-Associated Mutations Occur?.......................................... How Many Different Cancer Genes Are There?.......................................... How Many Cancer Genes Are Required for the Development of Cancer?........................................................................................................... Cancer Genetics Shapes our Understanding of Metastasis........................ Tumors Are Genetically Heterogeneous........................................................ Beyond the Exorne: The “Dark Matter” of the Cancer Genome.............. Further Reading................................................................................................. Cancer Gene Pathways............................. What Are Cancer Gene Pathways?................................................................. Cellular Pathways Are Defined by Protein-Protein Interactions............... Individual Biochemical Reactions, Multistep Pathways, and Networks..................................................................................................... Protein Phosphorylation Is a Common Regulatory Mechanism............... Signals from the Cell Surface: Protein Tyrosine
Kinases........................... Membrane-Associated GTPases: The RAS Pathway.................................. An Intracellular Kinase Cascade: The МАРК Pathway............................. Genetic Alterations of the RAS Pathway in Cancer.................................... Membrane-Associated Lipid Phosphorylation: The PI3K/AKT Pathway............................................................................................................... Control of Cell Growth and Energetics: The mTOR Pathway.................. Genetic Alterations in the PI3K/AKT and mTOR Pathways Define Roles in Cell Survival.......................................................................... The STAT Pathway Transmits Cytokine Signals to the Cell Nucleus............................................................................................................... Morphogenesis and Cancer: The WNT/APC Pathway............................... Dysregulation of the WNT/APC Pathway in Cancers................................ Notch Signaling Mediates Cell-to-Cell Communication............................ Morphogenesis and Cancer: The Hedgehog Pathway................................. TGF-ß/SMAD Signaling Maintains Adult Tissue Homeostasis................ MYC Is a Downstream Effector of Multiple Cancer Gene Pathways . . . P53 Activation Is Triggered by Damaged or Incompletely Replicated Chromosomes................................................................................. P53 Is Controlled by Protein Kinases Encoded by Tumor Suppressor
Genes................................................................................................................... P53 Induces the Transcription of Genes That Suppress Cancer Phenotypes................................................................ Feedback Loops Dynamically Control p53 Abundance............................ 195 195 196 196 199 201 202 203 203 205 208 210 211 211 213 215 217 220 225 227 228 230 232 235 236 238 239 242 243 245 247 250 253 257 26θ
Contents The DNA Damage Signaling Network Activates Interconnected Repair Pathways.......................................................................................... Inactivation of the Pathways to Apoptosis in Cancer............................... RB1 and the Regulation of the Cell Cycle................................................ Several Cancer Gene Pathways Converge on Cell Cycle Regulators ... Many Cancer Cells Are Cell Cycle Checkpoint Deficient....................... Chromatin Modification Is Recurrently Altered in Many Types of Cancer..................................................................................................... Putting Together the Puzzle....................................................................... Further Reading........................................................................................... 7 8 Cancer and the Immune System............................................................. Cancer Cells Express Unique Antigens..................................................... Tissue Homeostasis Requires Active Surveillance by the Immune System......................................................................................................... Understanding Immune Surveillance: The Innate and Adaptive Immune Responses to Influenza................................................................ Activation of Immune Signaling by Cytosolic DNA: The cGAS-STING Pathway....................................................................... Tumorigenesis Is Suppressed by Innate and Adaptive Immune
Mechanisms................................................................................................. The Seed and the Soil: Tumor Cells Shape Their Microenvironment. . . Dynamic Interactions Between Evolving Tumors and the Immune System: Immunoediting.............................................................................. Immunoediting During the Evolution of Multiple Myeloma................... Immune Checkpoints Restrain T-Cell Function........................................ Cancer Cells Activate Immune Checkpoints by Upregulating PD-L1.......................................................................................................... Tumors Produce Immunomodulatory Metabolites from Tryptophan. . . Immune Tolerance in Sun-Exposed Skin.................................................. Perspective: A Precarious Balance............................................................. Further Reading.......................................................................................... Common Cancers and Their Genetic Alterations................................ Cancer Genes Cause Diverse Diseases...................................................... Cancer Incidence, Prevalence, and Mortality............................................ LungCancer................................................................................................ Prostate Cancer........................................................................................... Breast Cancer..............................................................................................
Colorectal Cancer........................................................................................ Endometrial Cancer.................................................................................... Melanoma of the Skin................................................................................ Bladder Cancer............................................................................................ Lymphoma................................................................................................... Cancers in the Kidney................................................................................. xi 261 263 267 270 273 274 276 278 281 281 282 286 291 294 296 298 299 301 304 307 312 313 316 317 317 318 321 324 326 328 330 331 333 333 336
xii 9 10 Contents Thyroid Cancer......................................................................... Leukemia..................................................... Cancer in the Pancreas............................................................ Ovarian Cancer............................................ Cancers of the Oral Cavity and Pharynx............................. Liver Cancer....................................................................................................... Cancer of the Uterine Cervix................................................. Stomach Cancer........................................................................ Brain Tumors............................................................................ The Global Burden of Cancer in 2040........................................................... Further Reading................................................................................................. 338 339 341 343 344 346 347 348 349 351 353 Cancer Detection and Prognostication............................................................ 355 355 The Acquisition of DNA Sequence Data............................. Capturing the Complexity of Heterogeneous DNA Samples with Digital PCR...................................................................... Next-Generation Sequencing Mines the Full Information Content of DNA Samples................................................................................ Single-Molecule DNA Sequencing....................................... The Applications of Genetic
Data......................................... Decoding the Elements of Cancer Risk......................................................... Identifying Carriers of Germline Cancer Genes............... ........................... Biomarkers Facilitate the Detection of Early Stage Malignancies........... Cancer Genes as Biomarkers........................................................................... Liquid Biopsy Is a Tool for Disease Management...................................... 362 365 366 368 369 373 374 376 Mining the Information Content of Samples Obtained During Routine Screens................................................................................................. 37S Cancer Genes Are Versatile Biomarkers for Diagnosis, Prognosis, and Recurrence............................................................................... Assessing the T-Cell Response to Tumor Cells........................................... Incorporating Genetic Analysis into Routine Preventive Care.................. Further Reading................................................................................................. 379 381 385 386 Cancer Therapy........................................................................................................ Conventional Anticancer Therapies Inhibit Cell Growth............................ Therapeutic Inhibition of the Cell Cycle....................................................... Exploiting the Loss of DNA Repair Pathways: Synthetic Lethality .... On the Horizon: Achieving Synthetic Lethality in 7P53-Mutant
Cancers............................................................................................................... Molecularly Targeted Therapy: BCR-ABL and Imatinib............................ Evolution of Therapeutic Resistance.............................................................. Targeting EGFR Mutations............................................................................. Antibody-Mediated Inhibition of ReceptorTyrosine Kinases.................... Inhibiting Hedgehog Signaling....................................................................... Targeting the Pathways that Link KRAS to Cell Growth.......................... 359 389 389 392 397 399 401 4θ3 405 4θ6 407 410
Contents A Plethora of Rational Targets.................................................................. Dr. Coley’s Remedy of Mixed Toxins: The Birth of Immunotherapy . . Radiotherapy............................................................................................... The Mysterious Abscopal Effect: Radiotherapy as Immunotherapy .... Immune Checkpoint Blockade................................................................... Intrinsic Resistance to Immune Checkpoint Blockade Therapy.............. Acquired Resistance to Immune Checkpoint Blockade Therapy............. Personalized Oncology: Adoptive T-Cell Transfer.................................. Cancer Vaccines......................................................................................... The Future of Oncology............................................................................. Further Reading.......................................................................................... xiii 412 413 416 418 420 423 424 425 426 428 430
Fred Bunz Principles of Cancer Genetics This popular textbook, now in its third edition, provides a theoretical framework for understanding why cancers arise, how they develop and how they can be treated. Particular attention is devoted to the origins of cancer and the application of evolutionary theory to explain how mutant cell populations tend to expand and spread. Focused on the genes and signaling pathways involved in the most common tumors, Principles of Cancer Genetics is a highly readable account that will be of interest to anyone who would like to attain a basic understanding of cancer biology. Students who have completed introductory coursework in genetics, biology and biochemistry, medical students and medical house staffwill find this book to be a useful starting point toward master} of this complex but fascinating topic. This updated edition delves into the critical interactions between growing tumors and the immune system, and introduces the concepts of T cell activation, immunoediting and immune evasion. Novel strategies for cancer diagnosis and prognosis, including new roles for next-generation sequencing and liquid biopsies, as well as established and emerging therapeutic modalities are now described in detail. For laypersons, students and researchers in other fields with a general interest in cancer, this book provides an accessible overview, enriched with many easy-to֊understand il lustrations. For advanced students considering future study in the field ofoncology and cancer research, this concise book is a useful guide to the basic principles that
underlie our understanding of cancer.
|
| adam_txt |
ntents The Genetic Basis of Cancer. The Cancer Gene Theory. Cancers Are Invasive Tumors. Cancer Is a Unique Type of Genetic Disease. What Are Cancer Genes and How Are They Acquired?. Mutations Alter the Human Genome. Genes and Mutations. Single Nucleotide Substitutions. Gene Silencing Is Marked by Cytosine Methylation: Epigenetics. Environmental Mutagens, Mutations, and Cancer. Inflammation Promotes the Propagation of Cancer Genes. The Immune System Restrains Tumor Growth. Stem Cells, Darwinian Selection, and the Clonal Evolution of Cancers. Selective Pressure and Adaptation: Hypoxia and Altered Metabolism. Multiple Somatic Mutations Punctuate ClonalEvolution. Tumor Growth Leads to Cellular Heterogeneity. Tumors Are Distinguished by Their Spectrum of
Driver Gene Mutations and Passenger Gene Mutations. Colorectal Cancer: A Model for Understanding the Step-Wise Process of Tumorigenesis. Do Cancer Cells Divide More Rapidly Than Normal Cells?. Germline Cancer Genes Allow Neoplasia to Bypass Steps in Clonal Evolution. Cancer Syndromes Reveal Rate-Limiting Steps in Tumorigenesis. The Etiologic Triad: Heredity, the Environment, and Stem Cell Division. Understanding Cancer Genetics. Further Reading. 1 1 2 3 4 5 7 13 17 17 23 27 28 30 32 34 35 36 39 41 43 45 47 49 vii
viii 2 Contents Oncogenes. What Is an Oncogene?. The Discovery of Transmissible Cancer Genes. Viral Oncogenes Are Derived from the Host Genome. The Search for Activated Oncogenes: The RAS Gene Family. Complex Genomic Rearrangements: The MYC Gene Family. Proto-oncogene Activation by Gene Amplification. Proto-oncogenes Can Be Activated by Chromosomal Translocation . Chromosomal Translocations in Liquid Tumors. Chronic Myeloid Leukemia and the Philadelphia Chromosome. Oncogenic Activation of Transcription Factors in Prostate Cancer and Ewing’s Sarcoma. Oncogene Discovery in the Genomic Era: Mutations in PIK3CA. Selection of Tumor-Associated Mutations. Multiple Modes of Proto-oncogene Activation. Oncogenes Are Dominant Cancer Genes. Germline Mutations in RET and MET Confer Cancer Predisposition. Proto-oncogene Activation and Tumorigenesis. Further Reading. 3 Tumor
Suppressor Genes. What Is a Tumor Suppressor Gene?. The Discovery of Recessive Cancer Phenotypes. Retinoblastoma and Knudson’s Two-Hit Hypothesis. Chromosomal Localization of the Retinoblastoma Locus. The Mapping and Cloning of the Retinoblastoma Gene. Tumor Suppressor Gene Inactivation: The Second “Hit” and Loss of Heterozygosity. Recessive Genes, Dominant Traits. APC Inactivation in Inherited and Sporadic Colorectal Cancers. TP53 Is Frequently Inactivated During Tumorigenesis. Functional Inactivation of p53: Tumor Suppressor Genes and Oncogenes Interact. Mutant TP53 in the Germline: Li Fraumeni Syndrome. Gains-of-Function Caused by Cancer-Associated Mutations in TP53. Cancer Predisposition: Allelic Penetrance, Relative Risk and the Odds Ratio. Breast Cancer Susceptibility: BRCA 1 and BRCA2. Genetic Losses on Chromosome 9:
CDKN2A. Complexity at CDKN2A՛. Neighboring and Overlapping Genes. Genetic Losses on Chromosome 10: PTEN. SMAD4 and the Maintenance of Stromal Architecture. Two Distinct Genes Cause Neurofibromatosis. Patched Proteins Regulate Developmental Morphogenesis. 51 51 51 54 57 60 61 63 64 65 69 71 73 74 75 76 77 79 81 81 81 83 86 87 90 92 93 96 98 Ю0 103 104 HO 113 116 118 121 124 126
ontents ix von Hippel-Lindau Disease. NOTCHl: Tumor Suppressor Gene or Oncogene?. Multiple Endocrine Neoplasia Type 1. Most Tumor Suppressor Genes Are Tissue-Specific. Modeling Cancer Syndromes in Mice. Genetic Variation and Germline Cancer Genes. Tumor Suppressor Gene Inactivation During Colorectal Tumorigenesis. Inherited Tumor Suppressor Gene Mutations: Gatekeepers and Landscapers. Maintaining the Genome: Caretakers. Further Reading. 128 128 129 130 131 134 Genetic Instability and Cancer. What Is Genetic Instability?. The Majority of Cancer Cells Are Aneuploid. Aneuploid Cancer Cells Exhibit Chromosome Instability. Chromosome testability Arises Early in Colorectal Tumorigenesis . Chromosomal Instability Accelerates Clonal Evolution. Aneuploidy Can Result
from Mutations that Directly Impact Mitosis. STAG2 and the Cohesion of Sister Chromatids. Other Genetic and Epigenetic Causes of Aneuploidy. Transition from Tetraploidy to Aneuploidy during Tumorigenesis. Multiple Forms of Genetic testability in Cancer. Defects in Mismatch Repair Cause Hereditary Nonpolyposis Colorectal Cancer. Mismatch Repair-Deficient Cancers Have a Distinct Spectrum of Mutations. Defects in Nucleotide Excision Repair Cause Xeroderma Pigmentosum. NER Syndromes: Clinical Heterogeneity and Pleiotropy. DNA Repair Defects and Mutagens Define Two Steps Towards Genetic testability. Defects in DNA Crosslink Repair Cause Fanconi Anemia. A Defect in DNA Double Strand Break Responses Causes Ataxia-Telangiectasia. A Unique Form of Genetic testability Underlies Bloom Syndrome. Aging and Cancer: Insights from the Progeroid Syndromes. Instability at the End:
Telomeres and Telomerase. Overview: Genes and Genetic Stability. Further Reading. 141 141 142 145 147 148 135 138 139 140 149 151 153 154 156 158 163 165 171 172 174 178 182 185 188 191 192
x 5 6 Contents Cancer Genomes. Discovering the Genetic Basis of Cancer: From Genes to Genomes . What Types of Genetic Alterations Are Found in Tumor Cells?. How Many Genes Are Mutated in the Various Types of Cancer?. What Is the Significance of the Mutations that Are Found in Cancers?. When Do Cancer-Associated Mutations Occur?. How Many Different Cancer Genes Are There?. How Many Cancer Genes Are Required for the Development of Cancer?. Cancer Genetics Shapes our Understanding of Metastasis. Tumors Are Genetically Heterogeneous. Beyond the Exorne: The “Dark Matter” of the Cancer Genome. Further Reading. Cancer Gene Pathways. What Are Cancer Gene Pathways?. Cellular Pathways Are Defined by Protein-Protein Interactions. Individual Biochemical Reactions, Multistep Pathways, and Networks. Protein Phosphorylation Is a Common Regulatory Mechanism. Signals from the Cell Surface: Protein Tyrosine
Kinases. Membrane-Associated GTPases: The RAS Pathway. An Intracellular Kinase Cascade: The МАРК Pathway. Genetic Alterations of the RAS Pathway in Cancer. Membrane-Associated Lipid Phosphorylation: The PI3K/AKT Pathway. Control of Cell Growth and Energetics: The mTOR Pathway. Genetic Alterations in the PI3K/AKT and mTOR Pathways Define Roles in Cell Survival. The STAT Pathway Transmits Cytokine Signals to the Cell Nucleus. Morphogenesis and Cancer: The WNT/APC Pathway. Dysregulation of the WNT/APC Pathway in Cancers. Notch Signaling Mediates Cell-to-Cell Communication. Morphogenesis and Cancer: The Hedgehog Pathway. TGF-ß/SMAD Signaling Maintains Adult Tissue Homeostasis. MYC Is a Downstream Effector of Multiple Cancer Gene Pathways . . . P53 Activation Is Triggered by Damaged or Incompletely Replicated Chromosomes. P53 Is Controlled by Protein Kinases Encoded by Tumor Suppressor
Genes. P53 Induces the Transcription of Genes That Suppress Cancer Phenotypes. Feedback Loops Dynamically Control p53 Abundance. 195 195 196 196 199 201 202 203 203 205 208 210 211 211 213 215 217 220 225 227 228 230 232 235 236 238 239 242 243 245 247 250 253 257 26θ
Contents The DNA Damage Signaling Network Activates Interconnected Repair Pathways. Inactivation of the Pathways to Apoptosis in Cancer. RB1 and the Regulation of the Cell Cycle. Several Cancer Gene Pathways Converge on Cell Cycle Regulators . Many Cancer Cells Are Cell Cycle Checkpoint Deficient. Chromatin Modification Is Recurrently Altered in Many Types of Cancer. Putting Together the Puzzle. Further Reading. 7 8 Cancer and the Immune System. Cancer Cells Express Unique Antigens. Tissue Homeostasis Requires Active Surveillance by the Immune System. Understanding Immune Surveillance: The Innate and Adaptive Immune Responses to Influenza. Activation of Immune Signaling by Cytosolic DNA: The cGAS-STING Pathway. Tumorigenesis Is Suppressed by Innate and Adaptive Immune
Mechanisms. The Seed and the Soil: Tumor Cells Shape Their Microenvironment. . . Dynamic Interactions Between Evolving Tumors and the Immune System: Immunoediting. Immunoediting During the Evolution of Multiple Myeloma. Immune Checkpoints Restrain T-Cell Function. Cancer Cells Activate Immune Checkpoints by Upregulating PD-L1. Tumors Produce Immunomodulatory Metabolites from Tryptophan. . . Immune Tolerance in Sun-Exposed Skin. Perspective: A Precarious Balance. Further Reading. Common Cancers and Their Genetic Alterations. Cancer Genes Cause Diverse Diseases. Cancer Incidence, Prevalence, and Mortality. LungCancer. Prostate Cancer. Breast Cancer.
Colorectal Cancer. Endometrial Cancer. Melanoma of the Skin. Bladder Cancer. Lymphoma. Cancers in the Kidney. xi 261 263 267 270 273 274 276 278 281 281 282 286 291 294 296 298 299 301 304 307 312 313 316 317 317 318 321 324 326 328 330 331 333 333 336
xii 9 10 Contents Thyroid Cancer. Leukemia. Cancer in the Pancreas. Ovarian Cancer. Cancers of the Oral Cavity and Pharynx. Liver Cancer. Cancer of the Uterine Cervix. Stomach Cancer. Brain Tumors. The Global Burden of Cancer in 2040. Further Reading. 338 339 341 343 344 346 347 348 349 351 353 Cancer Detection and Prognostication. 355 355 The Acquisition of DNA Sequence Data. Capturing the Complexity of Heterogeneous DNA Samples with Digital PCR. Next-Generation Sequencing Mines the Full Information Content of DNA Samples. Single-Molecule DNA Sequencing. The Applications of Genetic
Data. Decoding the Elements of Cancer Risk. Identifying Carriers of Germline Cancer Genes. . Biomarkers Facilitate the Detection of Early Stage Malignancies. Cancer Genes as Biomarkers. Liquid Biopsy Is a Tool for Disease Management. 362 365 366 368 369 373 374 376 Mining the Information Content of Samples Obtained During Routine Screens. 37S Cancer Genes Are Versatile Biomarkers for Diagnosis, Prognosis, and Recurrence. Assessing the T-Cell Response to Tumor Cells. Incorporating Genetic Analysis into Routine Preventive Care. Further Reading. 379 381 385 386 Cancer Therapy. Conventional Anticancer Therapies Inhibit Cell Growth. Therapeutic Inhibition of the Cell Cycle. Exploiting the Loss of DNA Repair Pathways: Synthetic Lethality . On the Horizon: Achieving Synthetic Lethality in 7P53-Mutant
Cancers. Molecularly Targeted Therapy: BCR-ABL and Imatinib. Evolution of Therapeutic Resistance. Targeting EGFR Mutations. Antibody-Mediated Inhibition of ReceptorTyrosine Kinases. Inhibiting Hedgehog Signaling. Targeting the Pathways that Link KRAS to Cell Growth. 359 389 389 392 397 399 401 4θ3 405 4θ6 407 410
Contents A Plethora of Rational Targets. Dr. Coley’s Remedy of Mixed Toxins: The Birth of Immunotherapy . . Radiotherapy. The Mysterious Abscopal Effect: Radiotherapy as Immunotherapy . Immune Checkpoint Blockade. Intrinsic Resistance to Immune Checkpoint Blockade Therapy. Acquired Resistance to Immune Checkpoint Blockade Therapy. Personalized Oncology: Adoptive T-Cell Transfer. Cancer Vaccines. The Future of Oncology. Further Reading. xiii 412 413 416 418 420 423 424 425 426 428 430
Fred Bunz Principles of Cancer Genetics This popular textbook, now in its third edition, provides a theoretical framework for understanding why cancers arise, how they develop and how they can be treated. Particular attention is devoted to the origins of cancer and the application of evolutionary theory to explain how mutant cell populations tend to expand and spread. Focused on the genes and signaling pathways involved in the most common tumors, Principles of Cancer Genetics is a highly readable account that will be of interest to anyone who would like to attain a basic understanding of cancer biology. Students who have completed introductory coursework in genetics, biology and biochemistry, medical students and medical house staffwill find this book to be a useful starting point toward master}' of this complex but fascinating topic. This updated edition delves into the critical interactions between growing tumors and the immune system, and introduces the concepts of T cell activation, immunoediting and immune evasion. Novel strategies for cancer diagnosis and prognosis, including new roles for next-generation sequencing and liquid biopsies, as well as established and emerging therapeutic modalities are now described in detail. For laypersons, students and researchers in other fields with a general interest in cancer, this book provides an accessible overview, enriched with many easy-to֊understand il lustrations. For advanced students considering future study in the field ofoncology and cancer research, this concise book is a useful guide to the basic principles that
underlie our understanding of cancer. |
| any_adam_object | 1 |
| any_adam_object_boolean | 1 |
| author | Bunz, Fred ca. 20./21. Jh |
| author_GND | (DE-588)1301056235 |
| author_facet | Bunz, Fred ca. 20./21. Jh |
| author_role | aut |
| author_sort | Bunz, Fred ca. 20./21. Jh |
| author_variant | f b fb |
| building | Verbundindex |
| bvnumber | BV049086580 |
| classification_rvk | XH 4200 |
| classification_tum | BIO 000 |
| ctrlnum | (OCoLC)1343152986 (DE-599)BVBBV049086580 |
| dewey-full | 616.994 576.5 |
| dewey-hundreds | 600 - Technology (Applied sciences) 500 - Natural sciences and mathematics |
| dewey-ones | 616 - Diseases 576 - Genetics and evolution |
| dewey-raw | 616.994 576.5 |
| dewey-search | 616.994 576.5 |
| dewey-sort | 3616.994 |
| dewey-tens | 610 - Medicine and health 570 - Biology |
| discipline | Biologie Medizin |
| discipline_str_mv | Biologie Medizin |
| edition | Third edition |
| format | Book |
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| id | DE-604.BV049086580 |
| illustrated | Illustrated |
| index_date | 2024-07-03T22:28:47Z |
| indexdate | 2024-07-10T09:54:56Z |
| institution | BVB |
| isbn | 9783030993894 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-034348400 |
| oclc_num | 1343152986 |
| open_access_boolean | |
| owner | DE-384 |
| owner_facet | DE-384 |
| physical | XIII, 431 Seiten Illustrationen |
| publishDate | 2022 |
| publishDateSearch | 2022 |
| publishDateSort | 2022 |
| publisher | Springer |
| record_format | marc |
| spelling | Bunz, Fred ca. 20./21. Jh. Verfasser (DE-588)1301056235 aut Principles of cancer genetics Fred Bunz Third edition Cham Springer [2022] XIII, 431 Seiten Illustrationen txt rdacontent n rdamedia nc rdacarrier Cancer Genetics and Genomics Genetics Molecular Genetics Epigenetics Cancer Biology Cancer-Genetic aspects Molecular genetics Cancer Krebs Medizin (DE-588)4073781-0 gnd rswk-swf Genetik (DE-588)4071711-2 gnd rswk-swf Krebs Medizin (DE-588)4073781-0 s Genetik (DE-588)4071711-2 s DE-604 Erscheint auch als Online-Ausgabe 978-3-030-99387-0 Digitalisierung UB Augsburg - ADAM Catalogue Enrichment application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034348400&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis Digitalisierung UB Augsburg - ADAM Catalogue Enrichment application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034348400&sequence=000003&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA Klappentext |
| spellingShingle | Bunz, Fred ca. 20./21. Jh Principles of cancer genetics Cancer Genetics and Genomics Genetics Molecular Genetics Epigenetics Cancer Biology Cancer-Genetic aspects Molecular genetics Cancer Krebs Medizin (DE-588)4073781-0 gnd Genetik (DE-588)4071711-2 gnd |
| subject_GND | (DE-588)4073781-0 (DE-588)4071711-2 |
| title | Principles of cancer genetics |
| title_auth | Principles of cancer genetics |
| title_exact_search | Principles of cancer genetics |
| title_exact_search_txtP | Principles of cancer genetics |
| title_full | Principles of cancer genetics Fred Bunz |
| title_fullStr | Principles of cancer genetics Fred Bunz |
| title_full_unstemmed | Principles of cancer genetics Fred Bunz |
| title_short | Principles of cancer genetics |
| title_sort | principles of cancer genetics |
| topic | Cancer Genetics and Genomics Genetics Molecular Genetics Epigenetics Cancer Biology Cancer-Genetic aspects Molecular genetics Cancer Krebs Medizin (DE-588)4073781-0 gnd Genetik (DE-588)4071711-2 gnd |
| topic_facet | Cancer Genetics and Genomics Genetics Molecular Genetics Epigenetics Cancer Biology Cancer-Genetic aspects Molecular genetics Cancer Krebs Medizin Genetik |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034348400&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034348400&sequence=000003&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA |
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