Breast Medical Oncology Department, MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancer Metastasis Rev. 2012 Jun;31(1-2):247-68. doi: 10.1007/s10555-011-9342-8.
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.
有几个观察结果使我们提出了一个新的癌症机制假说。首先，癌症似乎只出现在那些具有复杂伤口愈合能力的多细胞生物中。其次，在临床上所有癌症中都可以发现被认为是风险因素的伤口。最后，癌基因的激活不仅出现在癌症中，也出现在正常生理和非癌症病理过程中。我们提出的假说认为，癌症是一种自然的与伤口愈合相关的过程，包括癌基因激活、细胞因子分泌、干细胞募集分化和组织重塑。伤口激活了一些细胞的癌基因，后者分泌细胞因子招募干细胞来修复伤口。然而，如果伤口的原因持续存在，例如在持续的紫外线和致癌物暴露下，持续的伤口愈合过程将导致临床癌症肿块。自然界中没有系统可以在伤口存在的中期停止或逆转伤口愈合过程。癌症机制的结果要么是愈合伤口，要么是耗尽整个系统（死亡）。这个假说有助于理解许多源自突变理论的癌症之谜，例如为什么尽管在 DNA 复制过程中所有多细胞生物都面临潜在的突变风险，但癌症只存在于一小部分多细胞生物中。这个假说可以用来解释和指导癌症的预防、复发、转移、体外和体内研究以及个性化治疗。
