Efnisyfirlit

• Cover
• Title Page
• Publisher’s Notice
• Copyright
• About the Authors
• Dedication
• Preface
• A Note to the Reader on the Third Edition
• Digital Resources for Instructors and Students
• Acknowledgments
• Table of Contents
• Detailed Contents
• Chapter 1: The Biology and Genetics of Cells and Organisms
• 1.1 Mendel establishes the basic rules of genetics
• 1.2 Mendelian genetics helps to explain Darwinian evolution
• 1.3 Mendelian genetics governs how both genes and chromosomes behave
• 1.4 Chromosomes are altered in most types of cancer cells
• 1.5 Mutations causing cancer occur in both the germ line and the soma
• 1.6 Genotype embodied in DNA sequences creates phenotype through proteins
• 1.7 Gene expression patterns also control phenotype
• 1.8 Modification of chromatin proteins and DNA controls gene expression
• 1.9 Unconventional RNA molecules also affect the expression of genes
• 1.10 Metazoa are formed from components conserved over vast evolutionary time periods
• 1.11 Gene cloning techniques revolutionized the study of normal and malignant cells
• Additional Reading
• Supplementary Sidebars
• Chapter 2: The Nature of Cancer
• 2.1 Tumors arise from normal tissues
• 2.2 Tumors arise from many specialized cell types throughout the body
• 2.3 Some types of tumors do not fit into the major classifications
• 2.4 Cancers seem to develop progressively
• 2.5 Tumors are monoclonal growths
• 2.6 Cancers occur with vastly different frequencies in different human populations
• 2.7 The risks of cancers often seem to be increased by assignable influences, including lifestyle
• 2.8 Specific chemical agents can induce cancer
• 2.9 Both physical and chemical carcinogens act as mutagens
• 2.10 Mutagens may be responsible for some human cancers
• 2.11 Synopsis and prospects
• Key Concepts, Thought Questions, and Additional Reading
• Supplementary Sidebars
• Chapter 3: Cancer as an Infectious Disease
• 3.1 Peyton Rous discovers a chicken sarcoma virus
• 3.2 Rous sarcoma virus is discovered to transform infected cells in culture
• 3.3 The continued presence of RSV is needed to maintain transformation
• 3.4 Viruses containing DNA molecules are also able to induce cancer
• 3.5 Tumor viruses induce multiple changes in cell phenotype including acquisition of tumorigenicity
• 3.6 Tumor virus genomes persist in virus-transformed cells by becoming part of host-cell DNA
• 3.7 Retroviral genomes become integrated into the chromosomes of infected cells
• 3.8 A version of the src gene carried by RSV is also present in uninfected cells
• 3.9 RSV exploits a kidnapped cellular gene to transform cells
• 3.10 The vertebrate genome carries a large group of proto-oncogenes
• 3.11 Slowly transforming retroviruses activate proto-oncogenes by inserting their genomes adjacent to these cellular genes
• 3.12 Some retroviruses naturally carry oncogenes
• 3.13 Bacterial cancers
• 3.14 Synopsis and prospects
• Key Concepts, Thought Questions, and Additional Reading
• Supplementary Sidebars
• Chapter 4: Cellular Oncogenes
• 4.1 Transfection of DNA provides a strategy for detecting nonviral oncogenes
• 4.2 Oncogenes discovered in human tumor cell lines are related to those carried by transforming retroviruses
• 4.3 Proto-oncogenes can be activated by genetic changes affecting either protein expression level or structure
• 4.4 Variations on a theme: the myc oncogene can arise via at least three additional distinct mechanisms
• 4.5 A diverse array of structural changes in proteins can also lead to oncogene activation
• 4.6 Synopsis and prospects
• Key Concepts, Thought Questions, and Additional Reading
• Supplementary Sidebars
• Chapter 5: Growth Factors, Receptors, and Cancer
• 5.1 Normal metazoan cells control each other’s lives
• 5.2 The Src protein functions as a tyrosine kinase
• 5.3 The EGF receptor functions as a tyrosine kinase
• 5.4 An altered growth factor receptor can function as an oncoprotein
• 5.5 A growth factor gene can become an oncogene: the case of sis
• 5.6 Transphosphorylation underlies the operations of many receptor tyrosine kinases
• 5.7 Yet other types of receptors enable mammalian cells to communicate with their environment
• 5.8 Nuclear receptors sense the presence of low–molecular-weight lipophilic ligands
• 5.9 Integrin receptors sense association between the cell and the extracellular matrix
• 5.10 The Ras protein, an apparent component of the downstream signaling cascade, functions as a G-protein
• 5.11 Synopsis and prospects
• Key Concepts, Thought Questions, and Additional Reading
• Supplementary Sidebars
• Chapter 6: Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer
• 6.1 A signaling pathway reaches from the cell surface into the nucleus
• 6.2 The Ras protein stands in the middle of a complex signaling cascade
• 6.3 Tyrosine phosphorylation controls the location and thereby the actions of many cytoplasmic signaling proteins
• 6.4 SH2 and SH3 groups explain how growth factor receptors activate Ras and acquire signaling specificity
• 6.5 Ras-regulated signaling pathways: A cascade of kinases forms one of three important signaling pathways downstream of Ras
• 6.6 Ras-regulated signaling pathways: a second downstream pathway controls inositol lipids and the Akt/PKB kinase
• 6.7 Ras-regulated signaling pathways: a third downstream pathway acts through Ral, a distant cousin of Ras
• 6.8 The JAK–STAT pathway allows signals to be transmitted from the plasma membrane directly to the nucleus
• 6.9 Cell adhesion receptors emit signals that converge with those released by growth factor receptors
• 6.10 The canonical and non-canonical Wnt pathways control diverse cellular phenotypes
• 6.11 G-protein–coupled receptors can also drive normal and neoplastic proliferation
• 6.12 Four additional “dual-address” signaling pathways contribute in various ways to normal and neoplastic proliferation
• 6.13 The Hippo signaling circuit integrates diverse inputs to govern diverse cell phenotypes
• 6.14 Well-designed signaling circuits require both negative and positive feedback controls
• 6.15 Synopsis and prospects
• Key Concepts, Thought Questions, and Additional Reading
• Supplementary Sidebars
• Chapter 7: Tumor Suppressor Genes
• 7.1 Cell fusion experiments indicate that the cancer phenotype is recessive
• 7.2 The recessive nature of the cancer cell phenotype requires a genetic explanation
• 7.3 The retinoblastoma tumor provides a solution to the genetic puzzle of TSGs
• 7.4 Incipient cancer cells eliminate wild-type copies of TSGs by a variety of mechanisms
• 7.5 The Rb gene often undergoes loss of heterozygosity in tumors
• 7.6 Loss-of-heterozygosity events can be used to find TSGs
• 7.7 Promoter methylation represents an important mechanism for inactivating TSGs
• 7.8 TSGs and their encoded proteins function in diverse ways
• 7.9 The NF1 protein acts as a negative regulator of Ras signaling
• 7.10 APC facilitates egress of cells from colonic crypts
• 7.11 KEAP1 regulates cellular response to oxidative stress
• 7.12 Not all familial cancers can be explained by inheritance of mutant TSGs
• 7.13 Synopsis and prospects
• Key Concepts, Thought Questions, and Additional Reading
• Supplementary Sidebars
• Chapter 8: pRb and Control of the Cell Cycle Clock
• 8.1 Cell growth and division is coordinated by a complex array of regulators
• 8.2 Cells make decisions about growth and quiescence during a specific period in the G1 phase
• 8.3 Cyclins and cyclin-dependent kinases constitute the core components of the cell cycle clock
• 8.4 Cyclin–CDK complexes are also regulated by CDK inhibitors
• 8.5 Viral oncoproteins reveal how pRb blocks advance through the cell cycle
• 8.6 pRb is deployed by the cell cycle clock to serve as a guardian of the restriction-point gate
• 8.7 E2F transcription factors enable pRb to implement growth-versus-quiescence decisions
• 8.8 A variety of mitogenic signaling pathways control the phosphorylation state of pRb
• 8.9 The Myc protein governs decisions to proliferate or differentiate
• 8.10 TGF-β prevents phosphorylation of pRb and thereby blocks cell cycle progression
• 8.11 pRb function and the controls of differentiation are closely linked
• 8.12 Control of pRb function is perturbed in most if not all human cancers
• 8.13 Synopsis and prospects
• Key Concepts, Thought Questions, and Additional Reading
• Supplementary Sidebars
• Chapter 9: p53: Master Guardian and Executioner
• 9.1 DNA tumor viruses lead to the discovery of p53
• 9.2 p53 is discovered to be a tumor suppressor gene
• 9.3 Inherited mutations affecting p53 predispose individuals to a variety of tumors
• 9.4 Mutant versions of p53 interfere with normal p53 function
• 9.5 p53 protein molecules usually have short lifetimes
• 9.6 Various signals cause p53 induction
• 9.7 DNA damage and deregulated growth signals cause p53 stabilization
• 9.8 Mdm2 destroys its own creator
• 9.9 ARF and p53-mediated apoptosis protect against cancer by monitoring intracellular signaling
• 9.10 p53 functions as a transcription factor that halts cell cycle advance in response to DNA damage and attempts to aid in the repair process
• 9.11 Prolonged DNA damage and oncogene activation can induce p53-dependent senescence
• 9.12 The apoptosis program participates in normal tissue development and maintenance
• 9.13 Apoptosis is a complex biochemical program that often depends on mitochondria
• 9.14 Both intrinsic and extrinsic apoptotic programs can lead to cell death
• 9.15 Cancer cells deploy numerous ways to inactivate their apoptotic machinery
• 9.16 p53 inactivation provides an advantage to incipient cancer cells at a number of steps in tumor progression
• 9.17 Additional forms of cell death may limit the survival of cancer cells
• 9.18 Synopsis and prospects
• Key Concepts, Thought Questions, and Additional Reading
• Supplementary Sidebars
• Chapter 10: Eternal Life: Cell Immortalization and Tumorigenesis
• 10.1 Normal cell populations appear to register the number of cell generations separating them from their ancestors in the early embryo
• 10.2 Cells need to become immortalized in order to form a cell line
• 10.3 Cancer cells need to become immortal in order to form tumors
• 10.4 The proliferation of cultured cells is also limited by the telomeres of their chromosomes
• 10.5 Telomeres are complex molecular structures that are not easily replicated
• 10.6 Incipient cancer cells can escape crisis by expressing telomerase
• 10.7 Telomerase plays a key role in the proliferation of human cancer cells
• 10.8 Some immortalized cells can maintain telomeres without telomerase
• 10.9 Telomeres play different roles in the cells of laboratory mice and in human cells
• 10.10 Telomerase-negative mice show both decreased and increased cancer susceptibility
• 10.11 The mechanisms underlying cancer pathogenesis in telomerase-negative mice may also operate during the development of human tumors
• 10.12 Synopsis and prospects
• Key Concepts, Thought Questions, and Additional Reading
• Supplementary Sidebars
• Chapter 11: Multi-Step Tumorigenesis
• 11.1 Most human cancers develop over many decades of time
• 11.2 Histopathology provides evidence of multi-step tumor formation
• 11.3 Cells accumulate genetic and epigenetic alterations as tumor progression proceeds
• 11.4 Cancer development seems to follow the rules of Darwinian evolution
• 11.5 Multi-step tumor progression helps to explain familial polyposis and field cancerization
• 11.6 Intra-tumor diversification can outrun Darwinian selection
• 11.7 Tumor stem cells further complicate the Darwinian model of clonal succession and tumor progression
• 11.8 Multiple lines of evidence reveal that normal cells are resistant to transformation by a single mutated gene
• 11.9 Human cells are constructed to be highly resistant to immortalization and transformation
• 11.10 Mammalian evolution contributed to the complexity of human cell transformation
• 11.11 Nonmutagenic agents, including those favoring cell proliferation, make important contributions to tumorigenesis
• 11.12 Mitogenic agents, key governors of human cancer incidence, can act as tumor promoters
• 11.13 Chronic inflammation often serves to promote tumor progression in mice and humans
• 11.14 Inflammation-dependent tumor promotion operates through defined signaling pathways
• 11.15 Metabolism is the elusive heart of the cancer process
• 11.16 Synopsis and prospects
• Key Concepts, Thought Questions, and Additional Reading
• Supplementary Sidebars
• Chapter 12: Shaping and Characterizing the Cancer Genome
• 12.1 Tissues are organized to minimize the progressive accumulation of mutations
• 12.2 The properties of stem cells make them good candidates to be cells-of-origin of cancer
• 12.3 Apoptosis, drug pumps, and DNA replication quality control mechanisms offer tissues a way to minimize the accumulation of mutant preneoplastic cells
• 12.4 Cell genomes are under constant attack from endogenous biochemical processes
• 12.5 Cell genomes are under occasional attack from exogenous mutagens and their metabolites
• 12.6 Cells deploy a variety of defenses to protect DNA molecules from attack by mutagens
• 12.7 Repair enzymes fix DNA that has been altered by mutagens
• 12.8 Inherited defects in nucleotide-excision repair, base-excision repair, and mismatch repair lead to specific cancer susceptibility syndromes
• 12.9 A variety of other DNA repair defects confer increased cancer susceptibility
• 12.10 The karyotype of cancer cells is often changed through alterations in chromosome structure
• 12.11 The karyotype of cancer cells is often changed through alterations in chromosome number
• 12.12 Advances in genome sequencing technologies have fueled a revolution in cancer genomics
• 12.13 Genomic analysis reveals that human cancers differ with respect to mutational burden, patterns of mutations, and copy number gains and losses
• 12.14 Cancer genomes contain driver and passenger gene mutations
• 12.15 Cancer genomic studies reveal both inter-tumoral and intra-tumoral heterogeneity
• 12.16 Synopsis and prospects
• Key Concepts, Thought Questions, and Additional Reading
• Supplementary Sidebars
• Chapter 13: Dialogue Replaces Monologue: Heterotypic Interactions and the Biology of Angiogenesis
• 13.1 Normal and neoplastic epithelial tissues are formed from interdependent cell types
• 13.2 The extracellular matrix represents a critical component of the tumor microenvironment
• 13.3 Tumors resemble wounded tissues that do not heal
• 13.4 Experiments directly demonstrate that stromal cells are active contributors to tumorigenesis
• 13.5 Macrophages and myeloid cells play important roles in activating the tumor-associated stroma
• 13.6 Endothelial cells and the vessels that they form ensure tumors adequate access to the circulation
• 13.7 Tripping the angiogenic switch is essential for tumor expansion
• 13.8 The angiogenic switch initiates a highly complex process
• 13.9 Anti-angiogenesis therapies have been employed to treat cancer
• 13.10 Nervous tissue contributes to tumor growth
• 13.11 Synopsis and prospects
• Key Concepts, Thought Questions, and Additional Reading
• Supplementary Sidebars
• Chapter 14: Moving Out: Invasion and Metastasis
• 14.1 The invasion–metastasis cascade begins with local invasiveness
• 14.2 Epithelial–mesenchymal transitions profoundly reshape the phenotypes of carcinoma cells
• 14.3 Epithelial–mesenchymal transitions are often induced by contextual signals
• 14.4 EMTs are programmed by transcription factors that orchestrate key steps of embryogenesis
• 14.5 Signals released by an array of stromal cell types contribute to the induction of invasiveness and intravasation
• 14.6 EMT-inducing transcription factors may enable entrance into the stem cell state
• 14.7 EMT-inducing transcription factors help drive malignant progression including metastatic dissemination
• 14.8 The invasiveness of carcinoma cells depends on clearance of obstructing ECM
• 14.9 Motility enables cancer cells to move into space excavated by MMPs
• 14.10 Intravasation and the formation of circulating tumor cells: first steps in perilous journeys
• 14.11 Colonization represents the most complex and challenging step of the invasion–metastasis cascade
• 14.12 Successful metastatic colonization often involves complex adaptations
• 14.13 An example of extreme metastatic specialization: metastasis to bone requires the subversion of osteoblasts and osteoclasts
• 14.14 Occult micrometastases threaten the long-term survival of many cancer patients
• 14.15 Synopsis and prospects
• Key Concepts, Thought Questions, and Additional Reading
• Supplementary Sidebars
• Chapter 15: Crowd Control: Tumor Immunology
• 15.1 The immune system continuously conducts surveillance of tissues
• 15.2 The human immune system plays a critical role in warding off various types of human cancer
• 15.3 The immune system functions to destroy foreign invaders and abnormal cells in the body’s tissues
• 15.4 The diversity of B cell and T cell receptors arises from the stochastic diversification of the genes that encode them
• 15.5 MHC molecules play key roles in antigen recognition by T cells
• 15.6 T cells that recognize MHC-I have different roles from those that recognize MHC-II
• 15.7 Dendritic cell activation of naive T cells is a key step in the generation of functional helper and cytotoxic T cells
• 15.8 Tumor antigens are targets of the immune response to cancer
• 15.9 Natural killer cells contribute to anti-cancer immunity
• 15.10 Macrophages make multiple contributions to tumor development
• 15.11 Regulatory T cells are indispensable negative regulators of the immune response that are co-opted by tumors to counteract immune attack
• 15.12 Immune checkpoints act to limit immune responses
• 15.13 Synopsis and prospects
• Key Concepts, Thought Questions, and Additional Reading
• Supplementary Sidebars
• Chapter 16: Cancer Immunotherapy
• 16.1 Vaccination can prevent cancer caused by infectious agents
• 16.2 Vaccination against human papillomaviruses prevents cervical cancer
• 16.3 Therapeutic vaccination is a potential treatment for cancer
• 16.4 Passive immunization with antibodies can be used to treat cancer
• 16.5 Lymphoma and breast cancer can be treated with monoclonal antibodies
• 16.6 Antibody–drug conjugates deliver toxic drugs to cells displaying tumor antigens
• 16.7 Cancer can be treated by adoptive cell transfer
• 16.8 CAR T cells have predetermined specificity and bypass MHC-dependent antigen presentation
• 16.9 Checkpoint inhibition is a distinct type of immunotherapy that modifies the behavior of immune cells
• 16.10 Checkpoint immunotherapies based on mouse studies have been applied in the oncology clinic
• 16.11 Resistance to immune checkpoint inhibitors commonly arises
• 16.12 Lethal encounters between T cells and cancer cells can be encouraged by constructing bi-specific antibodies
• 16.13 T-cell–dependent immunotherapies can be hampered by T-cell exhaustion
• 16.14 Synopsis and Prospects
• Key Concepts, Thought Questions, and Additional Reading
• Supplementary Sidebars
• Chapter 17: The Rational Treatment of Cancer
• 17.1 The development and clinical use of effective therapies will depend on accurate diagnosis of disease
• 17.2 Surgery, radiotherapy, and chemotherapy are the major pillars on which current cancer therapies rest
• 17.3 The present and future use of chemotherapy requires improved understanding of how anti-cancer drugs work
• 17.4 Differentiation, synthetic lethality, and cell cycle checkpoints can be exploited to kill cancer cells
• 17.5 Functional and biochemical considerations dictate that only a subset of the defective proteins in cancer cells are attractive targets for drug development
• 17.6 Pharmaceutical chemists can generate and explore the biochemical properties of a wide array of potential drugs
• 17.7 Drug candidates and their targets must be examined in cell models as an initial measurement of their utility in whole organisms
• 17.8 Studies of a drug’s action in laboratory animals are an essential part of pre-clinical testing
• 17.9 Promising candidate drugs are subjected to rigorous clinical tests in Phase I trials in humans
• 17.10 Phase II and III trials provide credible indications of clinical efficacy
• 17.11 Tumors often develop resistance to initially effective therapy
• 17.12 Targeting Bcl-2 to induce cell death
• 17.13 Gleevec paved the way for the development of many other highly targeted compounds
• 17.14 EGF receptor antagonists may be useful for treating a wide variety of tumor types
• 17.15 Proteasome inhibitors yield unexpected therapeutic benefit
• 17.16 B-Raf discoveries have led to inroads into the melanoma problem
• 17.17 Synopsis and prospects: challenges and opportunities on the road ahead
• Key Concepts, Thought Questions, and Additional Reading
• Supplementary Sidebars
• Abbreviations
• Glossary
• Index
• Supplementary Sidebars