Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26195756
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Proc+Natl+Acad+Sci+U+S+A
2015 ; 112
(29
): 8914-21
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Toward an evolutionary model of cancer: Considering the mechanisms that govern
the fate of somatic mutations
#MMPMID26195756
Rozhok AI
; DeGregori J
Proc Natl Acad Sci U S A
2015[Jul]; 112
(29
): 8914-21
PMID26195756
show ga
Our understanding of cancer has greatly advanced since Nordling [Nordling CO
(1953) Br J Cancer 7(1):68-72] and Armitage and Doll [Armitage P, Doll R (1954)
Br J Cancer 8(1):1-12] put forth the multistage model of carcinogenesis. However,
a number of observations remain poorly understood from the standpoint of this
paradigm in its contemporary state. These observations include the similar
age-dependent exponential rise in incidence of cancers originating from
stem/progenitor pools differing drastically in size, age-dependent cell division
profiles, and compartmentalization. This common incidence pattern is
characteristic of cancers requiring different numbers of oncogenic mutations, and
it scales to very divergent life spans of mammalian species. Also, bigger mammals
with larger underlying stem cell pools are not proportionally more prone to
cancer, an observation known as Peto's paradox. Here, we present a number of
factors beyond the occurrence of oncogenic mutations that are unaccounted for in
the current model of cancer development but should have significant impacts on
cancer incidence. Furthermore, we propose a revision of the current understanding
for how oncogenic and other functional somatic mutations affect cellular fitness.
We present evidence, substantiated by evolutionary theory, demonstrating that
fitness is a dynamic environment-dependent property of a phenotype and that
oncogenic mutations should have vastly different fitness effects on somatic cells
dependent on the tissue microenvironment in an age-dependent manner. Combined,
this evidence provides a firm basis for understanding the age-dependent incidence
of cancers as driven by age-altered systemic processes regulated above the cell
level.
free
free
free
