Abstract Cancer therapy is facing challenges. Since current theory could not have a breakthrough, we ought to find a new way to conquer cancer by exploring the emerging theory in cancer therapy. The complexity science, emerging in the 1980s, is the new stage of the system science development. It raises a series of transformation from humanities to natural science. Dissipative structure theory as a major science of complexity science, when applied to medical field, probable provide opportunity and inspiration referring to treatment. Dissipative structure theory, in brief, claims that a dissipative structure transform chaos to relatively stable non-equilibrium state through non-equilibrium phase transition. From the microscopic order, cancer composed by tumor cells is a dissipative structure, whose external environment is the human body. From the macroscopic order, the human body is a dissipative structure, whose external environment is the natural and social environment. The reason for tumor occurrence and progression is relatively non-equilibrium disrupted and negative entropy is not enough to correct high positive entropy. Survival with the tumor is to enhance negative entropy to resist highly positive entropy and then build a new relative non-equilibrium state. Innovative angle from the theory may enlighten us make the better use of dissipative structure theory in clinical cancer therapy.

1. HYPOTHESIS
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doi: 10.12032/TMR20190225104
Traditional Chinese Medicine
What are the challenges facing cancer therapy base on the dissipative
structure theory
Yue Yang1 #
, Ning-Ning Liu1,2 #
, Ming-Yu Sun2
*, Qi Li1
*
1
Department of Oncology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine;
Shanghai University of Traditional Chinese Medicine, Shanghai, China. 2
Key Laboratory of Liver and Kidney
Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese
Medicine, Shanghai, China.
*Corresponding to: Mingyu Sun, Key Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases,
Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. E-mail:
mysun248@hotmail.com. Qi Li, Department of Oncology, Shuguang Hospital Affiliated to Shanghai University of
Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Shanghai, China. E-mail:
lzwf@hotmail.com.
Highlights
Survival with the tumor is to enhance negative entropy to resist highly positive entropy and then build a
new relative non-equilibrium state.
Traditionality
The basic theories in traditional Chinese medicine (TCM) likes “YinYang” and “Tian Ren He Yi” are all
come from philosophy theory, which were recorded in the ancient book of Yijing and Zhuangzi (Zhou
Danasty of China, 1046 B.C.- 256 B.C.). “YinYang” theory insists “interdependence or balance between
Yin and Yang”.

2. HYPOTHESIS
83
Submit a manuscript: https://www.tmrjournals.com/tmr TMR | March 2019 | vol. 4 | no. 2 |
doi: 10.12032/TMR20190225104
Abstract
Cancer therapy is facing challenges. Since current theory could not have a breakthrough, we ought to find a new
way to conquer cancer by exploring the emerging theory in cancer therapy. The complexity science, emerging in
the 1980s, is the new stage of the system science development. It raises a series of transformation from humanities
to natural science. Dissipative structure theory as a major science of complexity science, when applied to medical
field, probable provide opportunity and inspiration referring to treatment. Dissipative structure theory, in brief,
claims that a dissipative structure transform chaos to relatively stable non-equilibrium state through
non-equilibrium phase transition. From the microscopic order, cancer composed by tumor cells is a dissipative
structure, whose external environment is the human body. From the macroscopic order, the human body is a
dissipative structure, whose external environment is the natural and social environment. The reason for tumor
occurrence and progression is relatively non-equilibrium disrupted and negative entropy is not enough to correct
high positive entropy. Survival with the tumor is to enhance negative entropy to resist highly positive entropy and
then build a new relative non-equilibrium state. Innovative angle from the theory may enlighten us make the better
use of dissipative structure theory in clinical cancer therapy.
Keywords: Dissipative structure theory, Complexity science, Oncology
Abbreviations:
TCM, Traditional Chinese medicine.
Competing interests:
The authors declare that there is no conflict of interests regarding the publication of this paper.
Citation:
Yang Y, Liu NN, Sun MY et al. What are the challenges facing cancer therapy base on the dissipative structure
theory. Traditional Medicine Research 2019, 4(2): 82-90.
Executive Editor: Cui-Hong Zhu.
Submitted: 9 July 2018, Accepted: 3 August 2018, Online: 10 September 2018.

3. HYPOTHESIS
84
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doi: 10.12032/TMR20190225104
Background
Cancer therapy is a tough problem. With the
development of genomics, proteomics and
metabolomics, high-flux molecular detection and
nanomedicine, cancer therapy becomes increasingly
diversified and individualized. However, shortcomings
in existing theory such as reductionism is apparently
and issues such as the relationship between tumor
development and tumor microenvironment, immune
response mechanisms and tumor interstitial
heterogeneity etc. are not thoroughly inquired [1-6].
Cancer is still unable to conquer but faces numerous
challenges. To this end, theory renovation of cancer
therapy is extremely necessary [7-9]. The complexity
science is a new science with multidisciplinary and
frontier of scientific research, which provides fresh air
for medical development [10-16]. As the main school
of complexity science, dissipative structure theory
reveals the unity of human body itself and its external
factors, generates theoretical basis for medical mode
conversion [17-19]. To interpret the occurrence,
progression and treatment of cancer from dissipative
structure theory, this paper attempts to put forward a
hypothesis that the dissipative structure theory can be
applied to cancer therapy and can probe into the new
direction of it.
Hypotheses sources
Mr. Stephen Hawking predicted that "the 21st century
was a century of complexity science". The complexity
science, as forefront of contemporary scientific
development, is continuously moving towards
unprecedented prosperity [20-23]. Dissipative structure
theory, as a major genus of complexity science, is a
nonlinear and open system away from the equilibrium
state. It changes internal parameters of the system by
exchanging materials and energy with environment
[24-27]. Once the threshold is reached, fluctuation
mechanism might be triggered and the "critical points"
could be crossed to occur non-equilibrium phase
transformation. Additionally, chemical oscillation such
as self-organization phenomena may result in a great
alteration from original chaotic disordered to relatively
non-equilibrium state in time, space or function [28-33].
In brief, dissipative structure theory considers
"non-equilibrium is the source of order".
"Non-equilibrium" is neither “unbalanced” nor
“balanced”, but a steady state infinitely close to the
“critical point” [34-35]. Dissipative structure theory
resolves contradictions between the second law of
thermodynamics and the darwinian theory of evolution,
eliminates the gap between inorganic chemical
substance and organism, and finds out rules of
disorderly and orderly bi-directional transformation
[36-41]. Its founder, Pregogine, calls it "a new
dialogue between man and nature." [42-44]. Since
current theory can’t give new thought to treatment,
why not make some bold attempts to explore it from
the emerging dissipative structure theory?
Hypotheses contents
According to the concept of dissipative structure theory,
human body is a typical dissipative structure.
Maintaining dynamic non-equilibrium state can
continue life. Therefore, once pathogenic factors
disrupt or destroy the relative non-equilibrium even
accumulate to a certain threshold, the organism may
shift to disorder, resulting in various diseases and even
threaten life. The dissipative structure theory has its
specific criteria. The degree of non-equilibrium state in
dissipative structure can be measured by "entropy"
[45-48]. As an open system, when exchanged with the
external environment, effective substances obtained
from the outside make the energy continuously
increase, which input negative entropy flow. On the
contrary, ineffective substances released to the outside
make the energy decrease, which output positive
entropy flow [49-51]. Negative entropy is ordered,
positive entropy is disordered. Entropy increases is
from order to disorder while entropy decrease is from
disorder to order [52-55]. Rolf Landauer has
mentioned that erasure of information is a process of
dissipation, from this logic, and the progress that
limited positive entropy output to external is
irreversible [56-57]. Hence, the metabolic of the
organism always makes body in the state of low
entropy or negative entropy. As a dissipative structure,
the entropy value of the human body is the sum of the
entropy produced by life activity and interaction with
external environment. Life activity absorbs ordered
matter and introduces negative entropy through
Figure 1 Dissipative structure theory

4. HYPOTHESIS
85
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interacting, outputs positive entropy through
metabolizing excessive aging cells and tissues [58-60].
Negative entropy flow corrects body positive entropy
and guides body tends to be orderly. Always in a state
of low entropy or negative entropy keeps the life
activities normal operation [61-63] (Figure 1).
Applying the dissipative structure theory to cancer
therapy is to interpret it in an emerging theory and find
newly direction to treatment from non-equilibrium
state.
Hypotheses basis
Cell division and chromosome replication are in
accordance with the specific rules of the body. Once it
broken, chromosome division will be suppressed and
cell apoptosis pathway will be blocked. As we all know,
cell is the micro-structure of organism. The DNA as
transfer of genetic information in cells may be affected
by the mutation factor when microscopic order altered,
which could induce the gene mismatch, missing,
inserting or re-arrangement [64-66]. When original
DNA sequencing was undermined, newly synthesized
DNA structure will change accordingly, and it may be
passed down to the generations. Furthermore, this
could activate the original oncogene, or inactivate the
tumor suppressor gene in original cell, and translate the
previously distinct protein or abnormal proliferation of
normal proteins [67-68]. Besides, changes in the
microscopic may cause the deviation between the
protein synthesis and the information transmission in
cells. Any variation in amino acid arrangement and the
spatial configuration of proteins can lead to alteration
in protein, enzymes and nucleic acid functions, which
is difficult to reverse once it appears.
The cancer itself and the surrounding tissue carry
out the switch of matter, energy and information all the
time with its host-the human body. After reaching a
certain threshold, it will mutate to a new relative
non-equilibrium state. Thus, tumor is also a dissipative
structure [69-72]. It spontaneously forms channels like
neovascularization and lymphatic in exchange to
obtain more. Based on the characteristics of abnormal
proliferation of tumor cells, it is easy to be unbalanced
in the process of communicating with the normal cells
in surrounding areas. Under the action of blood
pressure gradient, tumor cells may be transferred
between the vessel wall and lymphatic. Blood friction
or viscous force allows metastasis appear complex and
unpredictable [73, 74]. Vascular and lymphatics spread
throughout the body and supply nutrients to organs, so
tumor cells can migrate with blood and lymphatic fluid
to everywhere. If it adhesion and colonization in the
target organs, then form the same type of secondary
tumor. From dissipative structure theory, this is the
probable reason of recurrence and metastasis of cancer.
The change of "entropy" in dissipative structure
theory can also explain the occurrence and
development of cancer. Organism, as the host of tumor,
is the external environment and provides the basis of
material and energy for the survival of tumor. Cancer
cannot be isolated from the organism. Once
carcinogenesis occurs, original cell homeostasis will be
ruined by emergence of abnormally proliferative tumor
cells. To construct a new dissipative structure,
organization will trigger the fluctuation mechanism,
initiate the non-linear action and realize the
cooperative operation of self-replication, amplification
and communication, so that internal entropy of the
body system is increasing [75, 76]. When positive
entropy created by tumor is too huge and the negative
entropy derived from external hard to counteract; the
cancer will develop further and a series of symptoms is
appearing step by step [77, 78]. In other words, when
system positive entropy increase, the negative entropy
is too little to resist highly positive entropy, may
contribute to the development of cancer.
The basic theories in traditional Chinese medicine
(TCM) likes “YinYang” and “Tian Ren He Yi” are all
come from philosophy theory, which were recorded in
the ancient book of Yijing and Zhuangzi (Zhou Danasty
of China, 1046 B.C.- 256 B.C.) [79, 80]. “YinYang”
theory insists “interdependence or balance between Yin
and Yang”. It underlines the opposite and unified
relationship. Although Yin and Yang are the two sides
of things, they are interdependent with each other;
under certain conditions they can realize mutual
transformation, which is similar to the dissipative
structure transforming chaos to relatively
non-equilibrium state through non-equilibrium phase
transition. “Tian Ren He Yi” theory emphasizes
“heaven and man are mutually responsive” and “the
integration of heaven and man” [81]. Human is not an
isolated person, but a person in nature and in society.
Just like the dissipative structure theory mentioned,
dissipative structure can change internal parameters of
the system by exchanging materials and energy with
environment. TCM attaches great importance to
holistic view, not to cure independent disease, but the
sick person. TCM, which can effectively improve the
quality of life and reduce recurrence and metastasis, is
an indispensable and irreplaceable part of cancer
therapy. Thus, the hypotheses that exploring cancer
therapy with dissipative structure theory provides a
theoretical support for the indispensible role of TCM
treatment in the comprehensive cancer therapy.
Cancer therapy and its future
As a dissipative structure, cancer sustains a relatively
non-equilibrium state in the switch of material, energy
and information. Since it cannot be completely
separated from the external environment, it cannot
ignore the influence of it, which locates us to inquiry
the cancer treatment from dissipative structure theory
[82, 83]. The external environment of cancer can be

5. HYPOTHESIS
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doi: 10.12032/TMR20190225104
divided into two levels: for one hand, from the
microscopic order, cancer composed by tumor cells is
a dissipative structure, whose external environment is
the human body. For another hand, from the
macroscopic order, the human body is a dissipative
structure, whose external environment is the natural
and social environment. The reason for occurrence and
progression of cancer is relatively non-equilibrium
disrupted and negative entropy is not enough to correct
high positive entropy. If we want to address the issue
from source, what we should do is to preserve the
stability of relatively non-equilibrium state. Applying
dissipative structure theory to comprehend is mainly to
enhance negative entropy to resist highly positive
entropy.
From microscopic order to maintain the relatively
non-equilibrium state
From the point of view of prevention, we should
inhibit the mutation of cells and reduce the possibility
of abnormal proliferation of tumor cells. However,
inhibition of gene mutation is temporarily hard to
accomplish in present, or can be a direction of research
in the future. How to control the mutated cells? How to
delay the progression of disease and prevent the further
deterioration? These are the critical problems that
require being resolved at present. Gene mutations
determined by genetic factors are potentially
irreversible; in addition to the rigorous screening of
offspring on the basis of the discovery of the previous
generation, universal genetic sequencing may supply
more information about genetic mutations, which is of
certain significance for early warning, regular review,
diagnosis and treatment.
From the perspective of treatment, existing
treatment options include: surgery, radiotherapy,
chemotherapy, targeted therapy, photo thermal therapy,
cryoablation, percutaneous radiofrequency ablation,
interventional therapy, immunotherapy, endocrine
therapy, TCM, acupuncture treatment, the joint
comprehensive treatment, etc. All of these is to cut
positive entropy of system or import negative entropy
from outside to counteract the highly positive entropy
[83-85]. Thereby, to optimize the cancer treatment and
smash the bottleneck, we should break the mindset of
thinking, experiment diverse approaches to diminish
positive entropy or gain negative entropy. According to
assessment of specific situation, refinement of
individual classification and reference to different
types of tumors, tumor staging, physical conditions,
subtype combined clinical and basic experiment should
be accurately established.
From macroscopic order to maintain the relatively
non-equilibrium state
From physiological considerations, life activities and
diet structure, emotional changes and living habits are
intimately linked. People in natural and social
circumstances could maintain their relative
on-equilibrium only to find the balance between
external factors and themselves [86, 87]. Taking the
influence of emotion for example, long-term mood
disorder may lead to neurological, endocrine and
immune system disorder. Especially when the immune
system is dysfunctional, neither organism can stop
normal cells from mutating into cancer cells, nor
timely identify and mobilize the whole immune system
to kill cancer cells. Adjusting the diet and psychology,
regular living habits can decline positive entropy to
maintain the relative non-equilibrium. Meanwhile,
psychotherapy and social therapy would also assist
cancer therapy by increasing negative entropy. People
who are good at communication and able to adapt to
social life might have a better openness of the
emotional system, a stronger participation in the social
environment. These people usually acquire greater
negative entropy to keep fit [88-91]. Cancer therapy
ought pursuit “people-oriented” and consider both
physiological and psychosocial factors of the patients.
Taking pathological into consideration, the
maintenance of life activities is intimately associated
with water-electrolyte, metabolism and acid-base
disturbances, pathogenic microorganisms and
infectious diseases. Apart from tumors, for the patient
with basic diseases such as hypertension and coronary
heart disease, whether the tolerance of cancer therapy
or the response to body's consumption will be greatly
weakened. Maintaining the whole body basic level in
steady state, vigorously treating other basic diseases,
and minimizing non-tumor diseases on body
consumption may reduce the system positive entropy
to achieve the goal of cancer therapy. It is also one of
the possible reasons for enhancing immunity,
improving the quality of life and prolonging survival
period of cancer patients.
Building a new relative non-equilibrium state
Explore assiduously, but we have not yet conquered
cancer. Do we have to eradicate the cancer? What shall
we do if we can't get rid of it? In the constant groping,
we found a new way; that is, survival with tumor,
which means stabilize the tumor and prolong the
survival period as long as possible to under the premise
of maintaining the body's reactivity to tumor. After all,
tumor-free status is not always converted to the
extension of survival. Blindly pursuit the tumor-free
survival and over-treatment cannot benefit all cancer
patients. On the contrary, chasing for the statue that
survive with the tumor can give both doctors and
patients confidence in treatment and improve the
quality of life to some extent. When relatively
non-equilibrium broken, cancer occurs and progresses
further. Hence, we may boldly conceive that if we
establish a new relatively non-equilibrium state, is it
possible to stay in the temporary stability, reduce the
hazard of recurrence and metastasis, and improve the

6. HYPOTHESIS
87
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quality of life?
In recognition of the established reality of tumor
existence, we attempt to set up a steady state for
remaining the coexistence of body and tumor by drug
and other treatment [92-93]. By constructing a new
relatively non-equilibrium state to increase negative
entropy from the inside, so that the organism can
obtain better quality of life and longer overall survival.
It is also a point that the dissipative structure theory
has told us.
Conclusion
Cancer therapy faces many challenges. From the
dissipative structure theory to explore the challenge of
cancer therapy, we get plenty of illuminations in the
emerging theory. Once positive entropy increases,
negative entropy is insufficient; negative entropy is
difficult to resist highly positive entropy; it may induce
the occurrence and progression of cancer. Discussing
the influence of dissipative structure theory on normal
organism, cancer and cancer therapy, broaden horizons
to cope with problem. Regrettably, dissipative structure
theory as a new theoretical system has not been widely
accepted and applied. The discussion on treatment of
cancer is limited, and how it be transformed into
specific methods or used in clinic is still a mystery. But
we can still boldly assume that dissipative structure
theory can find a new direction for cancer therapy. Be
optimistic, admit unknown, abandon linear stereotype
thinking and give adequate play to initiative and
creativity, we would apply dissipative structure theory
more flexibly in the future to lead us infinitely
approach to the destination of cure cancer.
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