A new hypothesis for the cancer mechanism

Abstract

Several observations have led us to a new hypothesis for cancer mechanism. First, that cancer appears only on those multicellular organisms with complicated wound-healing capacities. Second, that wounds considered as risk factors can be identified in all cancers in clinics. And finally, that oncogene activation appears not only in cancer, but also in normal physiology and noncancer pathology processes. Our proposed hypothesis is that cancer is a natural wound healing-related process, which includes oncogene activations, cytokine secretions, stem cell recruitment differentiation, and tissue remodeling. Wounds activate oncogenes of some cells and the latter secrete cytokines to recruit stem cells to heal the wounds. However, if the cause of the wound or if the wound persists, such as under the persistent UV and carcinogen exposures, the continuous wound healing process will lead to a clinical cancer mass. There is no system in nature to stop or reverse the wound healing process in the middle stage when the wound exists. The outcome of the cancer mechanism is either healing the wound or exhausting the whole system (death). The logic of this cancer mechanism is consistent with the rationales of the other physiological metabolisms in the body-for survival. This hypothesis helps to understand many cancer mysteries derived from the mutation theory, such as why cancer only exists in a small proportion of multicellular organisms, although they are all under potential mutation risks during DNA replications. The hypothesis can be used to interpret and guide cancer prevention, recurrence, metastasis, in vitro and in vivo studies, and personalized treatments.

Fig. 1

Timeline of cancer hypothesis or theories

Fig. 2

A scheme of the wound–oncogene–wound healing mechanism

Fig. 3

Relationship of wound incidence (blue), wound healing ability (green), and cancer incidence (red) with age in mammals. Wound incidence increases and wound healing ability decreases along with ages. Cancer, as a functional wound healing tissue, its incidence increases due to the increased wound incidences along with the age, but decreases due to the exhausted wound healing ability at very old ages. All data points are descriptive according to the references of [, –50]

Fig. 4

A scheme of wound, cancer, feedbacks, and treatments. Physical, chemical, or biological factors cause a wound. A cancer responds to the wound to heal it. If the wound stimulation is persistent, a positive feedback loop will be formed till the wound is healed or the whole body exhausted. Surgery, chemo, and radiation therapies can halt the positive feedback loop quickly but the treatments themselves are wound causes. If the wound is persistent, another cancer will reoccur or be induced. To cure the cancer, all three facets, positive feedback loop (caner mass), wounds and wound causes must be covered, although the latter two are more complicated and difficult. Plus sign indicates increasing, promotion or positive feedback. Minus sign indicates decreasing, reduction, or negative feedback

Fig. 5

Molecular regulations for the treatments of diseases including cancer. X-axis: doses of major treatment molecules. The optimal doses are between minimum and max (point B). Y-axis: the influences of all other possible molecular regulations in cancer treatments, from drugs, diets, life styles to psychological influences. Max Y means the best influences. Min Y means the worst influences. Z-axis: a disease, a cancer mass or cancerization. Min Z means disease free and max means the worst disease stages. A Disease (cancer)-free point reached by optimal X and max Y. Only at this situation, the disease (cancer) can be cured. B Partial clinical response point by optimal X, but minimal Y (correct major treatments but unfortunately with the influences of other wrong life style, etc.). C Partial clinical response point by maximal Y, but minimal X (wrong major treatments with the correct influences of life styles, etc.). Z = X ² − Y ² means that the treatment outcome depends the personalized molecular balances at multiple dimensions. Cancer-spontaneous regression can be considered the extreme example to reach the point a in this model

Fig. 6

General metastasis. The corresponding oncogenes that have activities in their physiological metabolisms in the remote tissues can be activated by persistently circulating wound molecules derived from the wounds and cancer related inflammations. The cells with persistent activated oncogenes will transform and over-proliferate, leading to another cancer mass on the remote site without the primary cancer cell migration

Fig. 7

Interactions of cancer-related biomarkers with age, wounds, and cancer. Each mean ± 2SD of many cancer-related markers at 20 years old is set to be the puberty range (the reference range for an adult). Beyond this, mean ± 2SD is set to be out-puberty-range (OPR). The normal OPR marker count baseline from relatively healthy people is increased along with age due to the wound accumulations and cell aging (green). Wounds make higher OPR marker counts above the baseline and a cancer makes the higher OPR marker counts towards to the baseline after the wound healing (red line). Point A is the apex of an abnormal marker count peak and may be a “false positive” point if the pathological and imaging diagnoses fail to find the cancer. Point B is the correction point after the wound healing and may be a “false negative or less sensitivity” point if the pathological and imaging diagnoses find the cancer. Different sampling times for populations lead to false positives or false negatives. By monitoring dynamic OPR marker counts, the cancerization status can be seen and personalized treatments can be guided toward the normal baseline till the cure of cancer