Cancer: the enemy from within: a comprehensive textbook of cancer’s causes, complexities and consequences
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| Beschreibung: | X, 330 Seiten Illustrationen, Diagramme |
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| 245 | 1 | 0 | |a Cancer: the enemy from within |b a comprehensive textbook of cancer’s causes, complexities and consequences |c Carolyn Compton, MD, PhD |
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Datensatz im Suchindex
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| adam_text | v Contents 1 The Nature and Origins of Cancer....................................................... 1 1.1 Why Study Cancer?........................................................................................... 2 1.2 Cancer: The Enemy from Within...................................................................... 6 1.3 Cancer: A Multistep, Progressive Developmental Process......................... 8 1A The Language of Cancer: Taxonomy and Terminology of Neoplasms...................................................................................... 14 References......................................................................................................... 23 2 Cancer Initiation, Promotion, and Progression 2.1 Cancer Development: A Multistep Process................................................... 26 2.2 Mutations in a Developing Cancer............................................................... 32 2.2.1 Oncogenes........................................................................................................ 35 2.2.2 Tumor Suppressor Genes................................................................................ 36 2.2.3 Other Cancer Driver Genes.............................................................................. 38 2.3 Cancer Development: Increasing Divergence from Normal Form and Function.......................................................................................... 39 2.4 Cancer Progression and the Multistep Metastatic Cascade...................... 43
References......................................................................................................... 48 49 and the Acquisition of Key Behavioral Traits................ 25 3 Understanding the Hallmark Characteristicsof Cancer......... 3.1 Hallmark Traits That Allow All Cancer Cells to Outcompete Normal Cells..................................................................................................... 51 3.2 Uncontrolled Drive to Divide......................................................................... 51 3.2.1 Cell Division in Normal Stem Ceils Is Tightly Controlled............................... 51 3.2.2 Cancer Cells Acquire a Continuous Uncontrolled Drive to Divide Through Oncogene Mutation........................................................................ 56 3.3 Lossof Mutation Management and Control in Cell Division.................... 57 3.4 liability to Maintain a Stable Morenai Genome.......................... 59 3.5 Resistant to Cell Death.................................................................................... 60 3.6 Unlimited Potential for Cell Division............................................................ 64 3.7 Ability to Metastasize..................................................................................... 65 3.7.1 Metastasis Is Cancer s Deadliest Trait............................................................. 65 3.7.2 The First Step Is Epithelial-Mesenchymal Transition.................................... 67 3.7.3 The Next Steps Involve Invasion, Intravasation, 3.7.4 The Final Step Is Mesenchymal-
EpithelialTransition 3.8 Induction of a Private Blood Supply............................................................. 70 3.9 Manipulation of Normal Cells in the Tumor Microenvironment.............. 71 3.9.1 Cancer Cells Exploit the Functions of Normal Cells in the Tumor 3.9.2 inflammatory Cells In ťneTumor Microenvironment Produce Factors That Support the Cancer’s Growth and Survival............................ 73 3.10 Escapeof Immune Detection and Destruction........................................... 74 Survival in Circulation, and Extravasation..................................................... and Survival on Foreign Turf......................................................................... Microenvironment........................................................................................... 3.10.1 Irnmunoediting............................................................................................... 3.10.2 Immune Checkpoint-Mediated Control of Immune Cells........................... 68 69 71 74 75
VI Contents 3.1Û3 Additional Ways of Eluding the Immune System........................................... 76 3.11 Alteration of Metabolism and Energetics...................................................... ՜1՜1 3.1 Ί.Ί Cancer Cells Use Normal Metabolic Pathways in Abnormal Ways............... 3.11.2 Cancer Cells Use Anaerobic Metabolism in the Presenceof Oxygen.......... 3.11.3 Cancer Cells Am Glucose Gluttons..................................................................... 3.11.4 Anaerobic Metabolism Has Many Benefícia! Side Effects for the Cancer................................................................ 3.11.5 77 77 70 79 Heterogeneity in Cellular Energetics Among Tumor Cells Provides Additional Advantages...................................................... 80 Resources.............................................................................................................. θΊ 4 A Short History of Cancer: How Did We Get Here?........................ 83 4.1 Progress in Understanding the Nature of Cancer.......................................... 84 4.2 Progress in the Understanding of Causes of Cancer..................................... 88 4.3 Progress in the Treatment of Cancer................................................................. 90 4.4 Progress in the Molecular Biology of Cancer................................................ 100 Resources............................................................................................................. 107 Who Gets Cancer and Why? What Are the 5 Consequences for Human Life and Longevity? How Can
We Intervene? How Can We Track Progress?............ 109 5.1 The Sources of Cancer-Causing Mutations.................................................... 119 5.2 Does This Cause Cancer? How Do You Prove It?............................................ 113 5.3 Lowering Personal Cancer Risk......................................................................... 117 5.4 Tracking Cancer Around the World, Insights into Causal Associations, and Opportunities for Global Cancer Control..................... 126 5.5 Prevention: The Biggest Opportunity and the HighestValue for Cancer Control....................................................... 133 References.......................................................................................................... 135 6 Screening for Cancer: Find it Early; Treat It Early; 6.1 Screening: Looking for Cancer in Normal People.......................................... 138 6.2 The Theory of Screening Versus the Reality of Screening.......................... 139 6.3 TheHarmsVersustheBenefitsofScreening................................................ 146 6.4 CurrentCancerScreening Recommendations............................................. 155 6.5 The Status of Cancer Screening Around the World..................................... 157 Save Lives.......................................................................................... 137 References.......................................................................................................... 159 7 Fundamentals of Cancer Diagnosis and Assessment.............. 7.1 Diagnosis of Cancer
in the Symptomatic Patient.......................................... 162 7.2 Finding the Cancer. Location, Location, and Location................................. 165 7.2.1 Technologies Using External Ionizing Radiation.............................................. 166 7.2.2 Technologies Using Radioactive Isotopes........................................................ 7.2.3 161 168 Technology Using Magnetic Fields and Radio Waves............................ . 171 7.2.4 Technology Using SoundWaveS.............. . .................................................... 173 7.3 Tissue Is the Issue: Pathological Diagnosis and Assessment.................... 175 7.3.1 Squamous Cell Carcinoma............................................................................. 130 7.3.2 Adenocarcinoma Carcinoma.......................................................... 180 74 The Preeminent and Overriding Importance of Cancer Stage................. 185 ,
VII Contents 7.5 Predicting the Future for the New Cancer Patient...................................... 188 7.6 RecapoftheStoryofCancertoThisPoint................................................... 194 Resources.......................................................................................................... 195 8 Local Therapy for Cancer....................................................................... 8.1 Treatment Strategy Following Diagnostic and Assessment........................ 198 8.2 Oncological Surgery......................................................................................... 201 8.2.1 Tissue-Conserving Surgery.............................................................................. 205 8.2.2 Intraoperative Pathology Consultation......................................................... 206 8.2.3 Minimally Invasive Surgery.............................................................................. 207 8.2.4 Robotic Surgery................................................................................................ 208 8.2.5 Cryosurgery, Electrocautery, and Laser-Induced Thermal Therapy............ 209 8.2.6 PhotodynamicTherapy (PDT)......................................................................... 209 8.2.7 Image-Guided Tumor Sclerosis, Tumor Embolization, 197 or Intra-tumoral Injection of Soluble Therapeutic Agents............. 210 8.3 Local Treatment of Cancer: Radiation Therapy.............................................. 212
Resources............................................................................................................ 222 9 Systemic Therapy for Cancer................................................................ 9.1 An Overview of Systemic Therapy.................................................................... 224 9.2 Agents Used in Systemic Therapy.................................................................... 229 9.3 Cytotoxic Chemotherapy................................................................................... 230 9.3.1 Alkylating Agents............................................................................................... 232 9.3.2 Antitumor Antibiotics........................................................................................ 233 9.3.3 The Antimetabolites......................................................................................... 234 9.3.4 The Topoisomerase Inhibitors......................................................................... 234 9.3.5 The Microtubule Inhibitors............................................................................... 235 223 9.4 CategoriesofSystemic Therapy: Hormone Therapy..................................... 235 9.5 Categories of Systemic Therapy: Targeted Therapy.......................................238 9.6 Categories of Systemic Therapy: Immunotherapy........................................ 245 9.6.1 Activation Immunomodulation...................................................................... 247 9.6.2 Anticancer
Vaccines......................................................................................... 247 9.6.3 Cell-Based Therapy........................................................................................... 248 9.6.4 Immune Checkpoint Blockade........................................................................ 250 9.6.5 Oncolytic Viral Therapies.................................................................................. 252 9.7 CategoriesofSystemic Therapy: OtherTypes................................................ 253 9.8 Common Realities for All Systemic Therapies................................................ 255 References.......................................................................................................... 256 10 Palliative Care, Hospice, and End of Life........................................ 10.1 An Overview of Palliative Care..................................................................... 260 10.2 The Underutilization of Palliative Care: Contributing Factors................ 262 10.3 The Undeniable Value Proposition of Palliative Care............................... 266 References....................................................................................................... 267 11 Development of New CancerTherapies.......................................... 269 11.1 An Overviewof Drug Development for Cancer Therapy......................... 272 11.1.1 Drugs Are Medicinal Substances That Are Federally Regulated................. 272 11.1.2 Cancer Drugs Are Developed for Systemic Treatment of Systemic
Disease............................................................................ 273 259
Vili Contents 11.1.3 Cancer Drug Development Has Evolved as a Public-Private Partnership........................................................................................... 274 11.1.4 Industry and Academia Work Together in Anticancer Drug Development............................................................................. 276 11.2 The Evolution of Cancer Drug Development.............................................. 11.2.1 Naturally Occurring Substances That Are Toxic for Dividing 276 Cells Have Long Been Exploited as Cancer Chemotherapies ........ 276 11.2.2 With Greater Understanding of Cancer Pathobiology Came the Development of Molecularly Targeted Anticancer Drugs...... 277 11.2.3 Immunotherapies Utilize Molecules Produced by Immune Cells orlmmuneCellsThemselvesas Therapeutic Agents.................... 278 11.2.4 Beware the Hype in Drug Development........................................................ 279 11.3 Steps in the Process of Drug Development............................................... 11.3.1 Discovery: The First Step is the Discovery Process in 279 Which New Candidate Agents with Potential Impact on Cancer Biology Are Identified......................................................................... 279 11.3.2 After Discovering a Candidate Anticancer Agent, Other Factors That May Influence Its Successful Development as a Therapy Must Be Considered........................................................................... 281 11.4 Preclinical Development:The Second Step................................................ 11.4.1 The Behaviorof the
Agent in Biological Systems Must Be 281 Understood in Detail......................................................................... 281 11.4.2 Animal Studies Are Regulated by the Federal Government and Must Be Both Scientifically Justified and Humanely Conducted........................................................................................... 283 11.4.3 Animal Testing Is Valuable But Not Infallible in Determining the Safety and Efficacy of a New Cancer Drug................................. 285 ì 1.4.4 The Ability to Guarantee Sufficient Quality, Quantity, and Consistency of a Drug in the Manufacturing Process Must Be Demonstrated Prior to Human Testing............................. 286 11.5 Clinical Testing: The Third Stepandthe Highest Bar................................ 11.5.1 Human Experimentation Is the Most Challenging, 286 Most Expensive, and Most Essential Part of New Therapy Development..................................................................................... 286 11.5.2 The All-Important First Step in a Clinical Trial Is the Scientific Design....... 287 11.5.3 Protocol Development, Approval, and Implementation Require the Coordinated Efforts of Investigators, Funders, and Regulators................................................................................................. 287 11.5.4 A Clinical Trial with a New Experimental Drug Requires FDA Approval to Transport the Drug to Trial Centers..................... 288 11.6 The Ethical Framework of Clinical Trials (Human Experimentation) ... 11.6.1 Historically, Experimentation on Human Beings
Has Not Always Been Done Ethically.......................................................................... 288 11.6.2 US Federal Law Protects the Subjects of Clinical Research......................... 11.7 The Randomized Controlled Trial (RCT): The Historic Gold 11.7.1 The RCT Is a Head-to-Head Comparison Between Standard for Phase III Clinical Trials.............................................. 290 Standard-of-Care Therapy Alone and Standard-of-Care Therapy Plus the Experimental Drug.............................................................. 288 290 288
Contents í L-...... IX 11.7.2 The Design of an RCTIs AH Important.......................................................... 290 11.7.3 Low Participation Rates of Adult Cancer Patients in Clinical Trials Are a Major Roadblock to Progress in Therapeutic Drug Development........................................................................... 292 11.7.4 Phase IV Clinical Trials Monitor the Real-World Use of an Approved Drug.................................................................................. 292 11.8 Critical Problems in Cancer Drug Development and Proposed 11.8.1 The Big Picture in Cancer Drug Development Is Not Pretty....................... 293 Solutions........................................................................................... 293 11.8.2 Clinical Trials Need Innovation...................................................................... 293 11.8.3 Scientific Rigor and Reproducibility Are Wanting in the Discovery Process............................................................................. 295 11.8.4 Drug Prices Are Soaring, But They May Bear Little Relationship to Their Value for Patients or Society................................................ 295 References...................................................................................................... 297 12 Cancer and Society................................................................................. 299 12.1 The Enormity of the Cancer Burden on Global Society........................... 301 12.1.1 Cancer Is a Major Threat to Human Life Around the
World......................... 301 12.1.2 Society Has Been Able to Impact the Death Toll from Lung Cancer Through Education and Public Policies.............................. 301 12.1.3 In the United States, the Costs of Cancer Care Are Rising Rapidly, and the Rate of Rise Is Soon Expected to Overtake That of Overall Medical Expenditures ........................................................................ 302 12.1.4 Even the Successes of Cancer Treatment Further Increase Costs.............. 304 12.1.5 Globally, Cancer Takes the Highest Human and Economic Toll on Society.................................................................................... 305 306 12.2 The Personal Burden of Cancer on Individuals........................................ 12.2.1 Cancer Has Financial Consequences for Patients......................................... 306 12.2.2 Cancer Has Significant and Varied Emotional and Psychological Effects on Patients............................................................................. 307 12.2.3 Cancer Survivors Face Significant Personal Burdens................................... 308 12.3 Canceras a Political Issue............................................................................. 309 12.3.1 Cancer Isan Issue That Pervades the Public Affairs of American Society in Multiple Ways and on Multiple Levels........................... 309 12.3.2 ThePoliticsofCancerExtend Around the World......................................... 309 12.4 Cancer asa Big Business............................................................................... 12.4.1
Treating Cancer Is Profitable, Even If It Isn t Very Effective........................... 311 311 12.4.2 In the Cancer Business, the Profit Motive May Conflict with and Override the Public Good.......................................................... 311 12.5 Cancer as a Legal Issue................................................................................. 12.5.1 Many Personal and Societal Aspects of Cancer Intersect with the Law...................................................................................... 314 12.5.2 The Legal Right to End One s Life Electively and to Control the Circumstances of One s Death when Demise Is Inevitable Has Been Championed by Cancerpatients..................................... 314 12.5.3 The Legal Right to Have Access to Experimental Therapies If No Proven Therapies Existând Death Is Inevitable Has Been Championed by Cancer Patients..................................................... 316 314
Contents X 12.5.4 The Nascent Era of Genome Sequencing and Other Medical Technologies Has Raised New Legal Issues About Medical Liability That HaveYet to Be Fully Defined........................................................................ 12.5.5 That Roseto the Level of the US Supreme Court.............................. 12.6 317 The Legal Right to Patent Cancer Genes Sparked a Legal Struggle 318 Epilogue..................................................................................................................... 319 References................................................................................................................. 320 Correction to: Cancer: The Enemyfrom Within.............................. C1 Supplementary Information Index............................................................................................................................ The original version of this book was revised. The correction to this book can be found at https://doi.org/10.1007/978-3-030-40651-6_13 325
Carolyn Compton, MD, PhD Cancer: The Enemy from Within A Comprehensive Textbook of Cancer s Causes, Complexities and Consequences Ihis comprehensive, ground-breaking title presents, in simplifying style, the driving and organizing principles of cancer, making this multidimensional, highly complex disease easily understandable for readers. Developed out of the renowned author’s many years of teach ing a widely popular, several-hundred-student college course, this 12-chapter book begins with an account of the history of cancer as a medical and public health problem, as well as the major milestones and setbacks in the ongoing quest to understand the wide variety of cancers that continue to impact the world. Subsequent chapters then address pathogenesis, incidence and mortality statistics, risk factors, causal factors, screening challenges and victories, treatment strate gies, and disease prevention approaches. Ihis wealth of clinical infor mation is further supplemented with socioeconomic discussions on the financial, social, ethical, technological, regulatory, political, and logistical challenges that limit progress in cancer research. A soon to be gold-standard text that thoroughly and expertly describes cancer as a composite, adaptive system, Cancer: The Enemy from Within equips and empowers all undergraduate students and graduate students to better understand this continually perplexing disease. Clinicians across all disciplines may also find this work of great interest.
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v Contents 1 The Nature and Origins of Cancer. 1 1.1 Why Study Cancer?. 2 1.2 Cancer: The Enemy from Within. 6 1.3 Cancer: A Multistep, Progressive Developmental Process. 8 1A The Language of Cancer: Taxonomy and Terminology of Neoplasms. 14 References. 23 2 Cancer Initiation, Promotion, and Progression 2.1 Cancer Development: A Multistep Process. 26 2.2 Mutations in a Developing Cancer. 32 2.2.1 Oncogenes. 35 2.2.2 Tumor Suppressor Genes. 36 2.2.3 Other Cancer Driver Genes. 38 2.3 Cancer Development: Increasing Divergence from Normal Form and Function. 39 2.4 Cancer Progression and the Multistep Metastatic Cascade. 43
References. 48 49 and the Acquisition of Key Behavioral Traits. 25 3 Understanding the Hallmark Characteristicsof Cancer. 3.1 Hallmark Traits That Allow All Cancer Cells to Outcompete Normal Cells. 51 3.2 Uncontrolled Drive to Divide. 51 3.2.1 Cell Division in Normal Stem Ceils Is Tightly Controlled. 51 3.2.2 Cancer Cells Acquire a Continuous Uncontrolled Drive to Divide Through Oncogene Mutation. 56 3.3 Lossof Mutation Management and Control in Cell Division. 57 3.4 liability to Maintain a Stable Morenai Genome. 59 3.5 Resistant to Cell Death. 60 3.6 Unlimited Potential for Cell Division. 64 3.7 Ability to Metastasize. 65 3.7.1 Metastasis Is Cancer's Deadliest Trait. 65 3.7.2 The First Step Is Epithelial-Mesenchymal Transition. 67 3.7.3 The Next Steps Involve Invasion, Intravasation, 3.7.4 The Final Step Is Mesenchymal-
EpithelialTransition 3.8 Induction of a Private Blood Supply. 70 3.9 Manipulation of Normal Cells in the Tumor Microenvironment. 71 3.9.1 Cancer Cells Exploit the Functions of Normal Cells in the Tumor 3.9.2 inflammatory Cells In ťneTumor Microenvironment Produce Factors That Support the Cancer’s Growth and Survival. 73 3.10 Escapeof Immune Detection and Destruction. 74 Survival in Circulation, and Extravasation. and Survival on Foreign Turf. Microenvironment. 3.10.1 Irnmunoediting. 3.10.2 Immune Checkpoint-Mediated Control of Immune Cells. 68 69 71 74 75
VI Contents 3.1Û3 Additional Ways of Eluding the Immune System. 76 3.11 Alteration of Metabolism and Energetics. ՜1՜1 3.1 Ί.Ί Cancer Cells Use Normal Metabolic Pathways in Abnormal Ways. 3.11.2 Cancer Cells Use Anaerobic Metabolism in the Presenceof Oxygen. 3.11.3 Cancer Cells Am Glucose Gluttons. 3.11.4 Anaerobic Metabolism Has Many Benefícia! Side Effects for the Cancer. 3.11.5 77 77 70 79 Heterogeneity in Cellular Energetics Among Tumor Cells Provides Additional Advantages. 80 Resources. θΊ 4 A Short History of Cancer: How Did We Get Here?. 83 4.1 Progress in Understanding the Nature of Cancer. 84 4.2 Progress in the Understanding of Causes of Cancer. 88 4.3 Progress in the Treatment of Cancer. 90 4.4 Progress in the Molecular Biology of Cancer. 100 Resources. 107 Who Gets Cancer and Why? What Are the 5 Consequences for Human Life and Longevity? How Can
We Intervene? How Can We Track Progress?. 109 5.1 The Sources of Cancer-Causing Mutations. 119 5.2 Does This Cause Cancer? How Do You Prove It?. 113 5.3 Lowering Personal Cancer Risk. 117 5.4 Tracking Cancer Around the World, Insights into Causal Associations, and Opportunities for Global Cancer Control. 126 5.5 Prevention: The Biggest Opportunity and the HighestValue for Cancer Control. 133 References. 135 6 Screening for Cancer: Find it Early; Treat It Early; 6.1 Screening: Looking for Cancer in Normal People. 138 6.2 The Theory of Screening Versus the Reality of Screening. 139 6.3 TheHarmsVersustheBenefitsofScreening. 146 6.4 CurrentCancerScreening Recommendations. 155 6.5 The Status of Cancer Screening Around the World. 157 Save Lives. 137 References. 159 7 Fundamentals of Cancer Diagnosis and Assessment. 7.1 Diagnosis of Cancer
in the Symptomatic Patient. 162 7.2 Finding the Cancer. Location, Location, and Location. 165 7.2.1 Technologies Using External Ionizing Radiation. 166 7.2.2 Technologies Using Radioactive Isotopes. 7.2.3 161 168 Technology Using Magnetic Fields and Radio Waves. . 171 7.2.4 Technology Using SoundWaveS. . . 173 7.3 Tissue Is the Issue: Pathological Diagnosis and Assessment. 175 7.3.1 Squamous Cell Carcinoma. 130 7.3.2 Adenocarcinoma Carcinoma. 180 74 The Preeminent and Overriding Importance of Cancer Stage. 185 ,
VII Contents 7.5 Predicting the Future for the New Cancer Patient. 188 7.6 RecapoftheStoryofCancertoThisPoint. 194 Resources. 195 8 Local Therapy for Cancer. 8.1 Treatment Strategy Following Diagnostic and Assessment. 198 8.2 Oncological Surgery. 201 8.2.1 Tissue-Conserving Surgery. 205 8.2.2 Intraoperative Pathology Consultation. 206 8.2.3 Minimally Invasive Surgery. 207 8.2.4 Robotic Surgery. 208 8.2.5 Cryosurgery, Electrocautery, and Laser-Induced Thermal Therapy. 209 8.2.6 PhotodynamicTherapy (PDT). 209 8.2.7 Image-Guided Tumor Sclerosis, Tumor Embolization, 197 or Intra-tumoral Injection of Soluble Therapeutic Agents. 210 8.3 Local Treatment of Cancer: Radiation Therapy. 212
Resources. 222 9 Systemic Therapy for Cancer. 9.1 An Overview of Systemic Therapy. 224 9.2 Agents Used in Systemic Therapy. 229 9.3 Cytotoxic Chemotherapy. 230 9.3.1 Alkylating Agents. 232 9.3.2 Antitumor Antibiotics. 233 9.3.3 The Antimetabolites. 234 9.3.4 The Topoisomerase Inhibitors. 234 9.3.5 The Microtubule Inhibitors. 235 223 9.4 CategoriesofSystemic Therapy: Hormone Therapy. 235 9.5 Categories of Systemic Therapy: Targeted Therapy.238 9.6 Categories of Systemic Therapy: Immunotherapy. 245 9.6.1 Activation Immunomodulation. 247 9.6.2 Anticancer
Vaccines. 247 9.6.3 Cell-Based Therapy. 248 9.6.4 Immune Checkpoint Blockade. 250 9.6.5 Oncolytic Viral Therapies. 252 9.7 CategoriesofSystemic Therapy: OtherTypes. 253 9.8 Common Realities for All Systemic Therapies. 255 References. 256 10 Palliative Care, Hospice, and End of Life. 10.1 An Overview of Palliative Care. 260 10.2 The Underutilization of Palliative Care: Contributing Factors. 262 10.3 The Undeniable Value Proposition of Palliative Care. 266 References. 267 11 Development of New CancerTherapies. 269 11.1 An Overviewof Drug Development for Cancer Therapy. 272 11.1.1 Drugs Are Medicinal Substances That Are Federally Regulated. 272 11.1.2 Cancer Drugs Are Developed for Systemic Treatment of Systemic
Disease. 273 259
Vili Contents 11.1.3 Cancer Drug Development Has Evolved as a Public-Private Partnership. 274 11.1.4 Industry and Academia Work Together in Anticancer Drug Development. 276 11.2 The Evolution of Cancer Drug Development. 11.2.1 Naturally Occurring Substances That Are Toxic for Dividing 276 Cells Have Long Been Exploited as Cancer Chemotherapies . 276 11.2.2 With Greater Understanding of Cancer Pathobiology Came the Development of Molecularly Targeted Anticancer Drugs. 277 11.2.3 Immunotherapies Utilize Molecules Produced by Immune Cells orlmmuneCellsThemselvesas Therapeutic Agents. 278 11.2.4 Beware the Hype in Drug Development. 279 11.3 Steps in the Process of Drug Development. 11.3.1 Discovery: The First Step is the Discovery Process in 279 Which New Candidate Agents with Potential Impact on Cancer Biology Are Identified. 279 11.3.2 After Discovering a Candidate Anticancer Agent, Other Factors That May Influence Its Successful Development as a Therapy Must Be Considered. 281 11.4 Preclinical Development:The Second Step. 11.4.1 The Behaviorof the
Agent in Biological Systems Must Be 281 Understood in Detail. 281 11.4.2 Animal Studies Are Regulated by the Federal Government and Must Be Both Scientifically Justified and Humanely Conducted. 283 11.4.3 Animal Testing Is Valuable But Not Infallible in Determining the Safety and Efficacy of a New Cancer Drug. 285 ì 1.4.4 The Ability to Guarantee Sufficient Quality, Quantity, and Consistency of a Drug in the Manufacturing Process Must Be Demonstrated Prior to Human Testing. 286 11.5 Clinical Testing: The Third Stepandthe Highest Bar. 11.5.1 Human Experimentation Is the Most Challenging, 286 Most Expensive, and Most Essential Part of New Therapy Development. 286 11.5.2 The All-Important First Step in a Clinical Trial Is the Scientific Design. 287 11.5.3 Protocol Development, Approval, and Implementation Require the Coordinated Efforts of Investigators, Funders, and Regulators. 287 11.5.4 A Clinical Trial with a New Experimental Drug Requires FDA Approval to Transport the Drug to Trial Centers. 288 11.6 The Ethical Framework of Clinical Trials (Human Experimentation) . 11.6.1 Historically, Experimentation on Human Beings
Has Not Always Been Done Ethically. 288 11.6.2 US Federal Law Protects the Subjects of Clinical Research. 11.7 The Randomized Controlled Trial (RCT): The Historic Gold 11.7.1 The RCT Is a Head-to-Head Comparison Between Standard for Phase III Clinical Trials. 290 Standard-of-Care Therapy Alone and Standard-of-Care Therapy Plus the Experimental Drug. 288 290 288
Contents í L-. IX 11.7.2 The Design of an RCTIs AH Important. 290 11.7.3 Low Participation Rates of Adult Cancer Patients in Clinical Trials Are a Major Roadblock to Progress in Therapeutic Drug Development. 292 11.7.4 Phase IV Clinical Trials Monitor the Real-World Use of an Approved Drug. 292 11.8 Critical Problems in Cancer Drug Development and Proposed 11.8.1 The Big Picture in Cancer Drug Development Is Not Pretty. 293 Solutions. 293 11.8.2 Clinical Trials Need Innovation. 293 11.8.3 Scientific Rigor and Reproducibility Are Wanting in the Discovery Process. 295 11.8.4 Drug Prices Are Soaring, But They May Bear Little Relationship to Their Value for Patients or Society. 295 References. 297 12 Cancer and Society. 299 12.1 The Enormity of the Cancer Burden on Global Society. 301 12.1.1 Cancer Is a Major Threat to Human Life Around the
World. 301 12.1.2 Society Has Been Able to Impact the Death Toll from Lung Cancer Through Education and Public Policies. 301 12.1.3 In the United States, the Costs of Cancer Care Are Rising Rapidly, and the Rate of Rise Is Soon Expected to Overtake That of Overall Medical Expenditures . 302 12.1.4 Even the Successes of Cancer Treatment Further Increase Costs. 304 12.1.5 Globally, Cancer Takes the Highest Human and Economic Toll on Society. 305 306 12.2 The Personal Burden of Cancer on Individuals. 12.2.1 Cancer Has Financial Consequences for Patients. 306 12.2.2 Cancer Has Significant and Varied Emotional and Psychological Effects on Patients. 307 12.2.3 Cancer Survivors Face Significant Personal Burdens. 308 12.3 Canceras a Political Issue. 309 12.3.1 Cancer Isan Issue That Pervades the Public Affairs of American Society in Multiple Ways and on Multiple Levels. 309 12.3.2 ThePoliticsofCancerExtend Around the World. 309 12.4 Cancer asa Big Business. 12.4.1
Treating Cancer Is Profitable, Even If It Isn't Very Effective. 311 311 12.4.2 In the Cancer Business, the Profit Motive May Conflict with and Override the Public Good. 311 12.5 Cancer as a Legal Issue. 12.5.1 Many Personal and Societal Aspects of Cancer Intersect with the Law. 314 12.5.2 The Legal Right to End One's Life Electively and to Control the Circumstances of One's Death when Demise Is Inevitable Has Been Championed by Cancerpatients. 314 12.5.3 The Legal Right to Have Access to Experimental Therapies If No Proven Therapies Existând Death Is Inevitable Has Been Championed by Cancer Patients. 316 314
Contents X 12.5.4 The Nascent Era of Genome Sequencing and Other Medical Technologies Has Raised New Legal Issues About Medical Liability That HaveYet to Be Fully Defined. 12.5.5 That Roseto the Level of the US Supreme Court. 12.6 317 The Legal Right to Patent Cancer Genes Sparked a Legal Struggle 318 Epilogue. 319 References. 320 Correction to: Cancer: The Enemyfrom Within. C1 Supplementary Information Index. The original version of this book was revised. The correction to this book can be found at https://doi.org/10.1007/978-3-030-40651-6_13 325
Carolyn Compton, MD, PhD Cancer: The Enemy from Within A Comprehensive Textbook of Cancer's Causes, Complexities and Consequences Ihis comprehensive, ground-breaking title presents, in simplifying style, the driving and organizing principles of cancer, making this multidimensional, highly complex disease easily understandable for readers. Developed out of the renowned author’s many years of teach ing a widely popular, several-hundred-student college course, this 12-chapter book begins with an account of the history of cancer as a medical and public health problem, as well as the major milestones and setbacks in the ongoing quest to understand the wide variety of cancers that continue to impact the world. Subsequent chapters then address pathogenesis, incidence and mortality statistics, risk factors, causal factors, screening challenges and victories, treatment strate gies, and disease prevention approaches. Ihis wealth of clinical infor mation is further supplemented with socioeconomic discussions on the financial, social, ethical, technological, regulatory, political, and logistical challenges that limit progress in cancer research. A soon to be gold-standard text that thoroughly and expertly describes cancer as a composite, adaptive system, Cancer: The Enemy from Within equips and empowers all undergraduate students and graduate students to better understand this continually perplexing disease. Clinicians across all disciplines may also find this work of great interest. |
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| spelling | Compton, Carolyn Verfasser (DE-588)1219177768 aut Cancer: the enemy from within a comprehensive textbook of cancer’s causes, complexities and consequences Carolyn Compton, MD, PhD Cham Springer [2021] X, 330 Seiten Illustrationen, Diagramme txt rdacontent n rdamedia nc rdacarrier Oncology Life Sciences, general Oncology Life sciences Krebs Medizin (DE-588)4073781-0 gnd rswk-swf (DE-588)4123623-3 Lehrbuch gnd-content Krebs Medizin (DE-588)4073781-0 s DE-604 Erscheint auch als Online-Ausgabe 978-3-030-40651-6 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=034568735&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=034568735&sequence=000003&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA Klappentext |
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| title | Cancer: the enemy from within a comprehensive textbook of cancer’s causes, complexities and consequences |
| title_auth | Cancer: the enemy from within a comprehensive textbook of cancer’s causes, complexities and consequences |
| title_exact_search | Cancer: the enemy from within a comprehensive textbook of cancer’s causes, complexities and consequences |
| title_exact_search_txtP | Cancer: the enemy from within a comprehensive textbook of cancer’s causes, complexities and consequences |
| title_full | Cancer: the enemy from within a comprehensive textbook of cancer’s causes, complexities and consequences Carolyn Compton, MD, PhD |
| title_fullStr | Cancer: the enemy from within a comprehensive textbook of cancer’s causes, complexities and consequences Carolyn Compton, MD, PhD |
| title_full_unstemmed | Cancer: the enemy from within a comprehensive textbook of cancer’s causes, complexities and consequences Carolyn Compton, MD, PhD |
| title_short | Cancer: the enemy from within |
| title_sort | cancer the enemy from within a comprehensive textbook of cancer s causes complexities and consequences |
| title_sub | a comprehensive textbook of cancer’s causes, complexities and consequences |
| topic | Oncology Life Sciences, general Oncology Life sciences Krebs Medizin (DE-588)4073781-0 gnd |
| topic_facet | Oncology Life Sciences, general Oncology Life sciences Krebs Medizin Lehrbuch |
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