The chromosomal imbalance theory of cancer : autocatalyzed progression of aneuploidy is carcinogenesis / David Rasnick.

Format:

Book

Author/Creator:

Rasnick, David William, 1948-

Language:

English

Subjects (All):

Carcinogenesis.

Cancer--Genetic aspects.

Cancer.

Aneuploidy.

Neoplasms--etiology.

Neoplasms--genetics.

Chromosomal Instability.

Mutagenesis.

Medical Subjects:

Neoplasms--etiology.

Neoplasms--genetics.

Aneuploidy.

Chromosomal Instability.

Mutagenesis.

Physical Description:

xviii, 341 pages : illustrations (some color) ; 24 cm

Place of Publication:

Enfield, NH : Science Publishers ; Boca Raton, FL : Distributed by CRC Press, [2012]

Summary:

Rasnick, who worked in the pharmaceutical/biotech industry to develop protease inhibitors and founded three biotech companies, explains the chromosomal imbalance (aneuploidy) theory of cancer, as opposed to the gene mutation theory. He describes how gene mutations are not powerful enough to cause cancer; how cancer is initiated and why progression takes years or decades; and the global or macroscopic characteristics that identify cancer: anaplasia, autonomous growth, metastasis, abnormal cell morphology, DNA indices from 0.5 to over 2, genetic instability, and the high level of membrane-bound and secreted proteins responsible for invasiveness and loss of contact inhibition. He explains the common failure of chemotherapy and why cancer cells often become drug resistant, measures for detecting cancer and monitoring its progression, and non-toxic strategies for therapy and prevention. Distributed by CRC Press. Annotation ©2012 Book News, Inc., Portland, OR (booknews.com)

Contents:

1 Introducing Cancer 1

2 Boveri's Theory of Cancer was Ahead of its Time 12

2.1 Aneuploidy theory "Got Lost" 17

3 Genesis of "The Enemy Within"? 22

3.1 Clonal cancer 29

3.2 Tumorigenic retroviruses 34

3.3 Dominate oncogenes 42

3.4 Tumor suppressor genes 46

3.5 Driver genes 50

4 Gene Mutation Theory of Cancer 54

4.1 "Carcinogens are mutagens" 56

4.2 Retroviral oncogenes 57

4.3 Are "cellular oncogenes" like retroviral oncogenes? 59

4.4 Updated gene mutation theory is popular but unconfirmed 63

4.4.1 Gene mutation theory cannot explain non-mutagenic carcinogens and tumor promoters 64

4.4.2 No cancer-specific gene mutations 65

4.4.3 "Causative" mutations are not clonal and not shared by all cells of a tumor 65

4.4.4 Mutant genes do not transform normal cells into cancer cells 66

4.4.5 Mutagenic carcinogens should cause instant transformation 68

4.4.6 Gene mutation should have reproducible consequences 70

4.4.7 Non-selective phenotypes are not compatible with gene mutation 71

4.4.8 Cancer causing genes are hard to reconcile with human survival 72

4.4.9 Mutator phenotype to the rescue 73

4.4.10 Gene mutation does not explain chromosome instability in cancer 76

4.4.11 Karotypic-phenotypic cancer cell variation is orders of magnitude higher than gene mutation rates 77

4.4.12 Cancer phenotypes are too complex for conventional mutations 78

4.4.13 Ubiquity of aneuploidy in cancer is not explained by the mutation theory 79

5 The Chromosomal Imbalance Theory of Cancer 85

5.1 Heuristic explanation of how chromosomal imbalance (and not gene mutation) generates cancer phenotypes 87

5.2 Aneuploidy causes chromosomal instability-the hallmark of cancer 89

5.3 Cancer is a progressive somatic aneuploidy syndrome 95

5.3.1 Exact correlations between aneuploidy and cancer 97

5.3.2 Origin of aneuploidy 98

5.3.3 Carcinogens induce aneuploidy 99

5.3.4 Carcinogenesis from aneuploidy is much more probable than via mutation 100

5.3.5 Multi-drug resistance and other complex phenotypes are more probable from aneuploidy than mutation 101

5.3.6 Preneoplastic aneuploidy 102

5.3.7 Cancer-"specific" (non-random) aneusomies 106

5.3.8 Clonal aneuploid karyotypes: stability within instability 108

5.3.9 Chromosomal instability is proportional to the degree of aneuploidy 112

5.3.10 Chromosomal instability drives cancer progression without gene mutation 113

5.3.11 Autocatalyzed progression of aneuplodiy 115

5.4 Quantitative analysis of how aneuploidy generates new cellular phenotypes 118

5.4.1 The effect of aneuploidy on genomic stability can be quantified 128

6 Theory of Chromosomal Imbalance Solves Mysteries and Paradoxes 132

6.1 Carcinogenesis is dependent on aneuploidy and not mutation 132

6.1.1 Mutations of cancer cells as a consequence of aneuploidy 135

6.1.2 Cancer is not heritable because aneuploidy is not 136

6.1.3 Long neoplastic latencies are due to slow progression of aneuploidy 138

6.1.4 High rates of karyotypic-phenotypic variations and "immortality" 144

6.1.5 Karyotypic evolution of cancer 145

6.1.6 The Phenotypes of genomically unstable cells are usually dominant 148

6.1.7 Cancer-"specific" chromosomal alterations 149

6.1.8 Cancer is a progressive somatic aneuploidy syndrome with complex phenotypes 150

6.1.9 Non-selective phenotypes such as multi-drug resistance 151

6.1.10 Paradox of karyotypic stability-within-instability of cancers 151

6.2 Autocatalyzed progression of aneuploidy is carcinogenesis 154

6.2.1 The Hayflick limit is due to the autocatalyzed growth of aneuploidy 155

6.2.2 The sigmoidal age distribution of human cancer 164

6.2.3 Tumor formation 168

6.2.4 Drug resistance is an inevitable consequence of aneuploidy 174

6.3 Aneuploidy causes the Warburg effect by increasing ATP demand 176

6.4 Balanced mitotic forces and species-specific sequential chromatid separation may govern the rate of transformation 180

6.5 Cancer vaccine is very unlikely 186

6.6 "Cancers are a genuine type of species" 188

7 New Perspectives for Cancer Prevention, Diagnosis and Therapy 195

7.1 International regulation of aneuploidy-inducing agents 199

7.2 Cancer detection 202

7.2.1 Quantification of aneuploidy for diagnosis and prognosis 204

7.2.2 Chromosomal imbalance theory applied to transcript microarray data 212

7.3 Cancer therapy 220

7.3.1 Spontaneous tumor disappearance 224

7.3.2 Induction of fever as cancer treatment 226

8 Conclusion 235.

Notes:

Includes bibliographical references (pages [240]-316) and index.

ISBN:

9781578087372

1578087376

OCLC:

752072348