A novel pathogenic classification of cancers

Sonnenschein, Carlos; Davis, Barbara J.; Soto, Ana M.

doi:10.1186/s12935-014-0113-9

Cited by 11 publications

(13 citation statements)

References 49 publications

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“…affect embryos during organogenesis [34]. The evidence already collected in this field is consistent with the notion that in addition to the above-referred documented instances of inherited and induced inborn errors of development (Induced IED), a percentage of sporadic cancers (about 98% of all clinical cancers) may have been initiated in the womb [36, 37].…”

Section: Part II a New Theory Of Cancer The Tissue Organization Fiesupporting

confidence: 70%

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An Integrative Approach Toward Biology, Organisms, and Cancer

Sonnenschein

Soto

2017

Methods in Molecular Biology

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Over the last two decades, we have challenged the hegemony of the somatic mutation theory of carcino-genesis (SMT) based on the lack of theoretical coherence of the premises adopted by its followers. We offered instead a theoretical alternative, the tissue organization field theory (TOFT), that is based on the premises that cancer is a tissue-based disease and that proliferation and motility is the default state of all cells. We went on to use a theory-neutral experimental protocol that simultaneously tested the TOFT and the SMT. The results of this test favored adopting the TOFT and rejecting the SMT. Recently, an analysis of the differences between the Physics of the inanimate and that of the living matter has led us to propose principles for the construction of a much needed theory of organisms. The three biological principles are(a) a default state, (b) a principle of variation, and (c) one of organization. The TOFT, defined as “development gone awry,” fits well within the principles that we propose for a theory of organisms. This radical conceptual change opened up the possibility of anchoring mathematical modeling on genuine biological principles. By identifying constraints to the default state, multilevel biomechanical explanations become as legitimate as the molecular ones on which other modelers that adopt the SMT rely. Expanding research based on the premises of our theory of organisms will enrich a comprehensive understanding of normal development and of the one that goes awry.

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Section: Part II a New Theory Of Cancer The Tissue Organization Fiesupporting

confidence: 70%

“…These neoplasms are what we have described as inherited inborn errors of development (Inherited IED) [34, 35]. In such offspring, all the cells in their respective morphogenetic fields carry those genomic mutations.…”

Section: Part II a New Theory Of Cancer The Tissue Organization Fiementioning

confidence: 99%

An Integrative Approach Toward Biology, Organisms, and Cancer

Sonnenschein

Soto

2017

Methods in Molecular Biology

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“…These findings, along with emerging epidemiological and experimental data, lend to the conclusion that cancer is “development gone awry” [17, 64, 68]. The xenoestrogen BPA represents a more recent model of how an EDC can cause cancer - BPA affects MG development in female rats exposed to it in utero and perinatally in a number of ways such as by accelerating fat pad maturation, changing the stromal composition, inducing ductal elongation, inhibiting lumen formation and altering the pattern of gene expression of both stroma and epithelium during fetal development.…”

Section: 00 What Is An Edc?mentioning

confidence: 95%

Environmental endocrine disruptors: Effects on the human male reproductive system

Sweeney

Hasan

Soto

et al. 2015

Rev Endocr Metab Disord

143

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Incidences of altered development and neoplasia of male reproductive organs have increased during the last 50 years, as shown by epidemiological data. These data are associated with the increased presence of environmental chemicals, specifically “endocrine disruptors,” that interfere with normal hormonal action. Much research has gone into testing the effects of specific endocrine disrupting chemicals (EDCs) on the development of male reproductive organs and endocrine-related cancers in both in vitro and in vivo models. Efforts have been made to bridge the accruing laboratory findings with the epidemiological data to draw conclusions regarding the relationship between EDCs, altered development and carcinogenesis. The ability of EDCs to predispose target fetal and adult tissues to neoplastic transformation is best explained under the framework of the tissue organization field theory of carcinogenesis (TOFT), which posits that carcinogenesis is development gone awry. Here, we focus on the available evidence, from both empirical and epidemiological studies, regarding the effects of EDCs on male reproductive development and carcinogenesis of endocrine target tissues. We also critique current research methodology utilized in the investigation of EDCs effects and outline what could possibly be done to address these obstacles moving forward.

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“…Both hereditary cancers and tumors arising in transgenic animals may indeed be viewed as a consequence of inborn inherited errors of development-the result of a process initiated by a germ-line mutation(s) in the genome of one or both gametes (sperm and/or ovum)-as opposed to sporadic cancers (Sonnenschein et al 2014a). The mutated genome of the resulting zygote will endow all the cells in the morphogenetic fields of the developing organism with such a genomic mutation(s).…”

Section: The Role Of Mutationsmentioning

confidence: 98%

“…Examples of this variety of inborn errors of development include retinoblastoma, Gorlin syndrome, xeroderma pigmentoso, BRCA-1 and-2 neoplasia, and many others (Garber and Offit 2005). Therefore, cancers arising from inborn errors of development should be considered as separate pathogenetic entities when compared to sporadic cancers, given that they 'emerge' from very different morphogenetic fields (Sonnenschein et al 2014a).…”

Section: The Role Of Mutationsmentioning

confidence: 99%

SMT and TOFT: Why and How They are Opposite and Incompatible Paradigms

Bizzarri

Cucina

2016

Acta Biotheor

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The Somatic Mutation Theory (SMT) has been challenged on its fundamentals by the Tissue Organization Field Theory of Carcinogenesis (TOFT). However, a recent publication has questioned whether TOFT could be a valid alternative theory of carcinogenesis to that presented by SMT. Herein we critically review arguments supporting the irreducible opposition between the two theoretical approaches by highlighting differences regarding the philosophical, methodological and experimental approaches on which they respectively rely. We conclude that SMT has not explained carcinogenesis due to severe epistemological and empirical shortcomings, while TOFT is gaining momentum. The main issue is actually to submit SMT to rigorous testing. This concern includes the imperatives to seek evidence for disproving one's hypothesis, and to consider the whole, and not just selective evidence.

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A novel pathogenic classification of cancers

Cited by 11 publications

References 49 publications

An Integrative Approach Toward Biology, Organisms, and Cancer

An Integrative Approach Toward Biology, Organisms, and Cancer

Environmental endocrine disruptors: Effects on the human male reproductive system

SMT and TOFT: Why and How They are Opposite and Incompatible Paradigms

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