Continuing from the previous part, this article examines cancer from the viewpoint of flow. The cited references follow the original manuscript.
The Fifth Layer Called Environment
The explanation up to here is not a narrative that denies existing treatment. Surgery is the most powerful means of directly removing a local tumor, radiation reduces the cells in domains surgery does not reach, anticancer drugs attack residual cells in the systemic circulation, and targeted therapy and immunotherapy have achieved astonishing results in particular molecular subtypes. These four pillars are the reality of modern oncology, and the environment-centered viewpoint does not reduce the value of these pillars.
The proposal of this part is not a pillar but a layer. It is the proposal to add one fifth layer, which changes the very environment in which the tumor grows, upon the map of treatment that the four pillars support. The name of this layer is environmental intervention, and its content is a bundle of several approaches that correct the four axes of the tumor microenvironment (hypoxia, acidosis, inflammation, gradient collapse). This approach is not a new invention. Over the past 20 years it has accumulated independently in several domains of clinical research, and the role of this layer is to gather those pieces into one picture.
The important point is the fact that this fifth layer does not compete with the preceding four pillars. Rather it is the opposite. When the environment improves, anticancer drugs reach better, the responsiveness of radiation rises, and the effect of immunotherapy is amplified. The first case of environmental intervention is vascular normalization.
The concept of vascular normalization, published in the journal Science in 2005 by Rakesh Jain of Harvard Medical School, is the bridge that directly connects this viewpoint to the clinic. Jain's core insight is as follows. Tumor blood vessels are abnormally many but at the same time abnormally poor in function. The vessel walls leak, the blood flow is irregular, and the distribution of the vessels is disordered. As a result, hypoxic regions arise inside the tumor, and anticancer drugs cannot reach these regions. Paradoxically, the conditions of treatment change in the direction of making the tumor's blood vessels more like normal rather than reducing them further.
This prediction has received considerable verification through the following 20 years of clinical research. The effect when an antiangiogenic agent such as bevacizumab (Avastin) is used together with an anticancer drug was reinterpreted not as a strategy of simply reducing blood vessels to starve the tumor to death, but as a mechanism that temporarily normalizes the blood vessels to improve the penetration of anticancer drugs and the access of immune cells. Jain's follow-up report published in the journal Cancer Cell synthesized this reinterpretation. The timing of treatment became important, and an approach of capturing the window of vascular normalization by imaging and administering anticancer drugs within that window entered clinical trials.
The second domain of changing the environment, that is, the most powerful among non-chemical interventions, is exercise. Over the past 10 years the clinical evidence in this field has shifted its center of gravity from scattered observation to systematic meta-analysis, and then to randomized controlled trials. The most decisive result is the CHALLENGE trial published in the New England Journal of Medicine in 2025. This multicenter randomized trial divided 889 people who had finished adjuvant chemotherapy after surgery for colorectal cancer (high-risk stage II or stage III) into a regular exercise program group and a health education group and followed them long-term, and reported the result that the five-year disease-free survival and overall survival were significantly higher in the exercise group (five-year disease-free survival 80.3% vs. 73.9%, HR 0.72). This result has the strongest clinical evidence in high-risk stage II and stage III colorectal cancer, and generalization to other cancer types is being verified through follow-up clinical trials.
The mechanism research exactly matches this clinical result. According to the report of Betof and others published in the Journal of the National Cancer Institute, regular aerobic exercise reduces the hypoxic regions within the tumor, improves vascular perfusion, and as a result raises the responsiveness of chemotherapy. Exercise lowers systemic inflammatory indicators, improves insulin sensitivity, and the myokines secreted from muscle directly affect the tumor environment. All these paths are coherent with environmental improvement.
Metabolic intervention draws a similar trajectory. According to the report of Goodwin and others published in the Journal of Clinical Oncology, among breast cancer patients the group with high fasting insulin levels had independently higher risks of recurrence and death. Since then countless follow-up studies have confirmed that obesity, metabolic syndrome, and hyperinsulinemia correlate with the prognosis of several cancer types, and the review of Pernicova and Korbonits published in the journal Nature Reviews Endocrinology analyzed observational studies suggesting the possibility that metformin reduces recurrence in colorectal, breast, and prostate cancer. However, since these materials are mostly centered on observational research, the clinical results are not consistent according to cancer type and patient group, and there is still large-scale clinical controversy about the anticancer effect of metformin. Nevertheless, the value as a strategy of blocking the energy path of cancer cells that have lost metabolic flexibility, and the direction that interventions improving the metabolic environment can change outcomes, remain valid.
The management of chronic inflammation is also upon the same map. C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR), systemic inflammatory indicators, are established as independent prognostic factors of survival in several solid cancers, and the colorectal cancer prevention effect of low-dose aspirin is being reviewed as one axis of primary prevention. The review of Cuzick and others published in the journal Annals of Oncology quantitatively compared the benefits and harms brought by the preventive use of low-dose aspirin in the general population, and confirmed once again the possibility of meaningfully reducing colorectal cancer onset and death. However, since long-term use of aspirin accompanies the risks of gastrointestinal bleeding and hemorrhagic stroke, its application as primary prevention requires an individual risk-benefit evaluation. The direction that interventions improving the environment, especially chronic inflammation, can change outcomes is clear, but it is not a prescription that can be uniformly applied to everyone.
If we gather these clinical grounds into one picture, it looks as follows. Exercise reduces hypoxia and gradient collapse, metabolic intervention lowers the insulin and growth-signal axis, and inflammation management alleviates the chronic wound state surrounding the tumor. All three approaches are interventions that do not kill the tumor cells themselves but make the soil in which the tumor grows different. No one of them alone can cure progressive cancer, but if this fifth layer is laid upon the existing four pillars, the possibility arises that the result of treatment changes. The reality of environment-centered intervention is not a new invention but the work of binding already ongoing clinical research into one stream. However, there are limits to the scope of application. The clinical evidence for exercise is most strongly established in a limited patient group such as stage II/III colorectal cancer, and it is difficult to generalize this result directly to other cancer types. The possibility that the same environmental principle operates in other cancer types as well is open, and follow-up studies verifying that possibility are in progress.
Let us point out one thing precisely. Environmental intervention belongs to the domain that blocks additional deposition and additional accumulation (β suppression). It is not the domain that directly removes already-formed microcalcification or ongoing cancer (γ removal). γ removal operates in earnest at the point when clinical medication enters. The recovery formula of the previous chapter, that β suppression and γ removal must operate as a multiplication for recovery to occur, applies here just the same.
[Figure 5] The Fifth Layer Called Environment: Environmental Intervention Laid upon the Four Pillars
| Layer | Content | Role | Clinical basis |
|---|---|---|---|
| 1 Surgery | Local removal | γ removal (direct) | Surgical standard |
| 2 Radiation | Reducing cells | γ removal | Radiation standard |
| 3 Anticancer, targeted, immune | Molecular target | γ removal | Modern oncology |
| 4 Vascular normalization | Flow restoration | Environmental intervention (β, γ reinforcement) | Jain 2005, 2014 |
| 5 Exercise, metabolism, inflammation | Soil improvement | β suppression | Courneya 2025, Cuzick 2020 |
The Same Root, the Same Solution: The Beginnings Differ but the Gate Passed Through Is the Same
The explanation up to now is by no means trying to deny existing cancer treatment methods. Surgery is the most powerful method of directly removing the cancer mass, and radiation reduces the cancer cells in places the surgical knife does not reach. Anticancer drugs go around the whole body finding and attacking hidden cancer cells, and targeted therapy and immunotherapy are producing astonishing results tailored to the characteristics of particular cancers. These four pillars are the core that sustains modern cancer treatment, and just because we consider the environment around the cancer important, the value of these pillars by no means falls.
What is proposed here is not to erect a new pillar but to raise one new "layer" upon the existing pillars. That is, upon the foundation that the four treatment pillars hold up, to add a fifth layer that changes the very soil and environment in which cancer grows. This layer can be called "environmental improvement treatment," and it binds into one the various methods that correct the bad environment around the cancer, such as oxygen shortage, acidification, chronic inflammation, and collapsed bodily balance. This is not an invention that suddenly popped out. It is the product of fitting into one big picture the facts steadily revealed over the past 20 years in several fields of medical research.
The important fact here is that this fifth layer is not in a competing relationship with the four pillars mentioned earlier. Rather it is the exact opposite. When the environment around the cancer improves, anticancer drugs seep deeper into the cancer cells, radiation treatment works far better, and the effect of immunotherapy also jumps greatly. The first case of thus changing the environment is precisely "vascular normalization."
This concept, published in the renowned journal Science in 2005 by Professor Rakesh Jain of Harvard Medical School, played the important role of a bridge connecting the idea of environmental improvement to actual treatment. His core realization is this. Around the cancer mass there are abnormally many blood vessels, but they hardly perform their function. The vessel walls leak continuously, the flow of blood is a mess, and the shape in which they extend is also jumbled. As a result the inside of the cancer mass becomes woefully short of oxygen, and even when anticancer drugs are administered they cannot reach there. Therefore, rather than trying to starve the cancer to death by unconditionally eliminating the blood vessels, it is a paradoxical principle that the conditions in which treatment works well are made by trimming the blood vessels a little closer to normal.
This prediction has been quite splendidly proven through several studies conducted over the past 20 years. The effect that appears when a vessel-suppressing drug such as Avastin is used together with a general anticancer drug was not simply cutting off the blood vessels going to the cancer and starving it to death. Rather, it was newly revealed to be the role of temporarily making the vascular state closer to normal, helping the anticancer drugs and our body's immune cells to charge well into the cancer mass.
The follow-up research published in the journal Cancer Cell organized this new interpretation well. Now the timing of treatment has become extremely important. A new treatment method of capturing, with special imaging, the optimal period when the blood vessels are momentarily normalized (the window of timing) and then intensively administering anticancer drugs at exactly that point has entered the actual trial stage.
The second method of changing the environment, and the most powerful weapon among methods that do not use medicine, is precisely "exercise." Over the past 10-some years the evidence in this field has moved its center of gravity beyond the level of simple observation to very systematic and rigorous large-scale comparative studies. The most decisive result came from a study (the CHALLENGE trial) published in 2025 in the New England Journal of Medicine, the world's highest-authority medical journal. This study divided 889 patients who had finished both surgery and chemotherapy for colorectal cancer into two groups. One side was made to follow a regular exercise program, and the other side received only general health education, and they were watched over a long period. As a result, the people who steadily exercised had a clearly higher probability of being alive and healthy without the cancer recurring for five years. This result is the most powerful evidence showing how important exercise is, especially for colorectal cancer patients at a particular stage, and additional studies confirming whether exercise produces such good effects in other kinds of cancer as well are currently actively in progress.
Studies that tracked the actual changes occurring inside our body also exactly match these results. According to research published in the Journal of the National Cancer Institute, regular aerobic exercise resolves the oxygen-shortage phenomenon inside the cancer mass and opens up the blood-vessel blockage, consequently making anticancer drugs work far better. Moreover, exercise calms the inflammation figures of the whole body, improves the insulin function that regulates blood sugar, and the beneficial substances gushing out from muscle directly exert good influence on the environment around the cancer. All these positive changes in the end connect perfectly with the goal of "making an environment where cancer is hard to grow."
"Metabolic management," which regulates our body's nutritional and energy state, also shows a similar flow. Looking at research published in the Journal of Clinical Oncology, among breast cancer patients those whose insulin levels were usually high had a far greater risk of cancer recurrence or death. In the countless studies that followed, it was also confirmed that when there is a problem in the body's energy management, as in obesity or metabolic syndrome, the treatment results of various cancers worsen.
Analysis results that "metformin," a commonly used diabetes medicine, might reduce the recurrence of colorectal, breast, or prostate cancer have also been published in renowned journals. Of course, since the results still appear differently according to the patient's situation and medical controversy remains, it is a stretch to conclude a diabetes medicine as a cancer treatment right away. Nevertheless, the direction that the effort of cutting off the food supply of cancer cells, which abnormally suck in energy, and returning our body's overall nutritional and metabolic environment to health can positively change cancer treatment results is very clear.
Managing chronic inflammation is also placed in the same context. That high chronic inflammation figures in our body, which can be known by blood tests, have a bad influence on the survival rate of many cancer patients is already widely known medically. Even the point that steadily taking a small dose of aspirin may help prevent colorectal cancer is being seriously reviewed.
Looking at research published in a related journal, when the benefits and side effects that ordinary people can obtain from taking low-dose aspirin for prevention were meticulously weighed, it was also confirmed that colorectal cancer onset and the death resulting from it can be meaningfully reduced. But since taking aspirin over a long period also accompanies the risk of side effects such as bleeding in the stomach or cerebral hemorrhage, not just anyone should take it indiscriminately, and one must weigh the gains and losses with a doctor according to one's own health state. In short, the direction that improving the bad environment of chronic inflammation hidden in the body can change the landscape of cancer treatment is certain, but it means it is not a magic prescription that can be applied to everyone as if stamped out identically.
If we gather into one picture the various medical grounds examined so far, it is as follows. Steady exercise fills in the oxygen shortage around the cancer and restores the collapsed bodily balance. A healthy diet and weight management block the signals, such as insulin, that grow cancer cells, and inflammation management soothes the state in which the area around the cancer mass keeps festering. All three of these methods do not directly cut out the cancer cells with a knife or kill them with poison, but they are interventions that transform the very "soil" in which the seed of cancer takes root and grows into a completely different environment. With this environmental improvement alone one cannot cure already-spread cancer at a stroke, but if this fifth layer is laid upon the existing four powerful treatment pillars, the possibility arises that the treatment result changes.
The reality of environment-centered intervention is not a new invention that did not exist in the world, but the work of threading already widely ongoing clinical research into one wisdom. Of course, there are still limits to the scope of application. The clinical basis for exercise is most strongly established in colorectal cancer patients at particular stages, and it is difficult to apply this result identically to all cancers. But the possibility that the same environmental principle, that a bad seed is hard to grow in good soil, operates in other cancer types as well is wide open, and follow-up studies verifying this are steadily in progress.
Lastly, let us point out one thing precisely. All these efforts to improve the environment belong to the domain of "suppression and defense," which blocks cancer cells from becoming more ingrained and piling up in our body. It is not the role of "active removal," which directly breaks and eliminates the cancer mass itself that has already firmly settled or is expanding its power. The direct removal of the cancer mass operates in earnest at the point when surgery or clinical medication is put in. The recovery formula of the previous chapter, that the defense that blocks a bad environment from piling up and the attack that directly eliminates the mass must interlock and turn together like a multiplication for full recovery to occur, applies just the same in this process of cancer treatment.
[Figure 6] The Progression of Cancer Seen Through the Five DTDMC Stages: The Beginnings Differ but the Gate Passed Through Is the Same
| Stage | Aging-related cancer | Cancer outside the boundary | Domain of intervention |
|---|---|---|---|
| 1 Determinant (D) | Accumulation of the DIAH trigger | Genetic, viral, developmental | β suppression (prevention) |
| 2 Trigger (T) | Appearance of precancerous lesion | Different primary beginning | β suppression (early intervention) |
| 3 Dual blockade (D) | Entry into the environmental blockade circuit | The same environmental blockade | Environmental intervention (the fifth layer) |
| 4 Manifestation (M) | Clinical tumor | Clinical tumor | Four pillars + environment |
| 5 Annihilation (C) | Metastasis, multi-organ failure | Metastasis, multi-organ failure | Palliative care |
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