Abstract
Surgery has contributed to unveil a tumor behavior that is difficult to reconcile with the models of tumorigenesis based on gradualism. The postsurgical patterns of progression include unexpected features such as distant interactions and variable rhythms. The underlying evidence can be summarized as follows: (1) the resection of the primary tumor is able to accelerate the evolution of micrometastasis in early stages, and (2) the outcome is transiently opposed in advanced tumors. The objective of this paper is to give some insight into tumorigenesis and surgery-related effects, by applying the concepts of the evolutionary theory in those tumor behaviors that gompertzian and tissular-centered models are unable to explain. According to this view, tumors are the consequence of natural selection operating at the somatic level, which is the basic mechanism of tumorigenesis, notwithstanding the complementary role of the intrinsic constrictions of complex networks. A tumor is a complicated phenomenon that entails growth, evolution and development simultaneously. So, an evo-devo perspective can explain how and why tumor subclones are able to translate competition from a metabolic level into neoangiogenesis and the immune response. The paper proposes that distant interactions are an extension of the ecological events at the local level. This notion explains the evolutionary basis for tumor dormancy, and warns against the teleological view of tumorigenesis as a process directed towards the maximization of a concrete trait such as aggressiveness.
Highlights
Surgery has contributed to unveil a tumor behavior that is difficult to reconcile with the models of tumorigenesis based on gradualism
I propose that, from the point of view of the tumor subclones, the ecological dynamics can be interpreted as follows: (1) a tumor patch containing an effective angiogenic phenotype tends to displace the rest of the clones; (2) the local expansion of the prevailing cells increases the selective pressure to the neighbors, primarily as a contest for neighboring resources, and later by inducing a stromal release of angiogenesis inhibitors; (3) when the dominant subclone expands to a critical level, the overflowing inhibitors exert local effects on the systemic setting [64]
The crucial questions are not related to the convenience of the evolutionary theory, but to the origin of those rhythms and the influences of multicellularity
Summary
If we ignore the biology of the tumors that we are removing, we will certainly not be able to explain the adaptations of the networks that remain. With a lower level of evidence, the same advantage seems to occur in other metastatic tumors, such as ovarian cancer [3], germ cell tumors [4], breast [5,6], and colorectal cancer [7] The reason behind these clinical findings could be due to one of the following: (1) the debulking of a huge mass; (2) the resection of a primary tumor that is qualitatively different from a metastasis; (3) the perturbation of diffuse interaction networks; (4) and, the prevention of local complications. Most women obtained a benefit from early diagnosis of a breast tumor, the pooled data of mammography trials reflected a paradoxical excess of relapse and death, in a subgroup of young patients with positive lymph nodes This observation was attributed to a potential iatrogenic effect of screening.
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