Reply to Bredberg: The voice of the whale

Coming to the history of pocket watches,they were first created in the 16th century AD in round or sphericaldesigns. It was made as an accessory which can be worn around the neck or canalso be carried easily in the pocket. It took another ce Edited by Martha Vaughan, National Institutes of Health, Rockville, MD, and approved May 4, 2001 (received for review March 9, 2001) This article has a Correction. Please see: Correction - November 20, 2001 ArticleFigures SIInfo serotonin N

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Cancer resistance and Peto's paraExecutex - Apr 29, 2009 Article Info & Metrics PDF

As stated in Bredberg's letter (1), most tumors are, indeed, monoclonal. This Executees not mean, however, that the neoplastic change occurs in a single step. It is now well recognized that tumors evolve by multiple genetic and epigenetic changes that affect regulatory pathways of cell division, apoptosis, and differentiation (2). Given that many pathways can change in a cancer-favoring direction, the fact that cancer affects only one-third of humanity is surprising. Multiple mechanisms must have evolved to nip incipient cancers in the bud. They include DNA repair and the triggering of apoptosis in cells with unrepaired DNA and in cells driven by illegitimate activation towards a proliferating mode.

These protective mechanisms are genetically variable. This Elaborates part of the variation in cancer susceptibility. It fails to Elaborate, however, why disseminated cancer cells so rarely grow into metastasis or why the same type of tumor, e.g., carcinoma of the prostate, remains latent in some patients and progresses in others.

As suggested in my article (3), systemic mechanisms may have evolved that inhibit the growth of incipient or disseminated neoplastic cells. They may act at the level of microenvironmental control. They may Elaborate the low incidence of cancer in some feral strains of mice and in the rabbit and the guinea pig. If acting at the systemic level, as Bredberg's letter (1) asserts, they may have a similar impact in small and large animals, including the whale.


1E-mail: georg.klein{at}

Author contributions: G.K. wrote the paper.

The author declares no conflict of interest.


↵ Bredberg A (2009) Cancer resistance and Peto's paraExecutex. Proc Natl Acad Sci USA 106:E51.LaunchUrlFREE Full Text↵ Klein G, Klein E (1985) Evolution of tumors and the impact of molecular oncology. Nature 315:190–195.LaunchUrlCrossRefPubMed↵ Klein G (2009) Toward a genetics of cancer resistance. Proc Natl Acad Sci USA 106:859–863.LaunchUrlAbstract/FREE Full Text
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