discussed the stochastic effect here. We have shown that the struc-
ture of the endogenous molecular-cellular network model is similar
to the Morse-Smale dynamical system [53]. Adaptive landscape is a
suitable quantity to describe the transition between the attractors,
the robustness of these attractors, the trajectory and escape time
from one attractor to another can be obtained from the landscape
intuitively. And recent progress on stochastic dynamical systems
[105–109] allows us to construct the adaptive landscape based on
the endogenous molecular-cellular network [110–112].3.4 Mutation Theory
and Endogenous
Network Theory:
Further Remarks
Cancer mutation theory is essentially a statistical approach based on
associations. Logically, it is not surprising that such a theory leads
to a conclusion prevailing in the current literature: Every cancer is a
complete different disease. There are enough mutations to do such
classification: there are 10^9 base pairs in our genome. As a compari-
son we know that a little more than 100 chemical elements is
already enough to make up the known material world. On the
other hand, endogenous network is a biologically mechanistic
dynamical theory. It assumes one network beyond all the observed
phenomena: normal and abnormal. It is a grand unification theory
in biology. We are not there yet: after more than 10 years’ effort we
have not reached the core network stage. The results already con-
vincingly suggest a common core for all cancers, just the opposite of
naively expected from the cancer mutation theory. In our view we
have now the technology to get this one endogenous network.
Though the two theories are apparently quite different, we
have already found that the endogenous network can predict muta-
tion patterns. The predictions at the core network level are vali-
dated by experiments. We would like to point out another
important prediction validated by the recent progress in cancer
research, so far completely overlooked. In 2011 the next generation
of cancer hallmarks was proposed [45]. An examination of the new
cancer hallmarks reveals that they were already anticipated by the
endogenous network theory. “Deregulating cellular energetics,”
“avoiding immune destruction,” and “tumor promoting inflamma-
tion” were directly anticipated in the 2008 endogenous network
proposal [26]. This counts for three out of four new hallmarks. The
remaining hallmark, “genetic instability and mutations,” was dis-
cussed earlier, even quantitatively [110]. It was not regarded as the
essential part of endogenous network theory, but as one of its
consequences. The recent prediction from the endogenous net-
work theory further supports this conclusion [56].
On the other hand, sticking to cancer mutation theory can lead
to confusions. The recent much circulated work based on such an
associated study is a good example of such confusion: they are lost
when anticipated correlation was not found between cancers and
mutations [113]: In our view those experts do not really know what
they are talking about, while such findings are easy to understandEndogenous Molecular-Cellular Network Cancer Theory 239