Preprint Hypothesis Version 1 Preserved in Portico This version is not peer-reviewed

On the Origin of Carcinoma

Version 1 : Received: 22 January 2021 / Approved: 25 January 2021 / Online: 25 January 2021 (15:31:18 CET)

How to cite: Mendez, F. On the Origin of Carcinoma. Preprints 2021, 2021010514. Mendez, F. On the Origin of Carcinoma. Preprints 2021, 2021010514.


The origin of cancer remains one of the most important enigmas in modern biology. The prevailing paradigm has failed to grasp a comprehensive view of the disease. Naturally, therapies developed under the current assumptions are inadequate and cancer is practically an incurable disease. Meanwhile, descriptive studies continuously extend the molecular complexity of cancer without an equivalent advancement in its understanding. Furthermore, they tend to accumulate inconsistencies inexplicable under the classical view. This paper presents a compelling theory of the origin of carcinomas. By hypothesis, a series of generic events in epithelial tissues promoted by cellular aging and inflammation enables the reactivation of developmental programs. The origin of carcinomas in vivo is described as the time-ordered cell state transitions undergone by epithelial cells in the hyperplasia due to replicative senescence and inflammation towards a mesenchymal undifferentiated endogenous cell state with cancerous behavior. In support of the theory, the molecular, cellular, and histopathological evidence is critically reviewed. A plausible model for the origin of carcinomas is presented to explain the mechanism underlying carcinogenesis from an evolutive and developmental perspective. The implications of the hypothesis in the current strategies for cancer prevention and treatment are discussed along with rational alternatives and some predictions for possible experimental validation.


Senescence; Immortalization; Epithelial to Mesenchymal Transition; Carcinogenesis; Hypothesis


Biology and Life Sciences, Biochemistry and Molecular Biology

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