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An evolutionary explanation for the perturbation of the dynamics of metastatic tumors induced by surgery and acute inflammation.

Carmona Bayonas A - Cancers (Basel) (2011)

Bottom Line: The postsurgical patterns of progression include unexpected features such as distant interactions and variable rhythms.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Medical Oncology, Hospital Morales Meseguer, Murcia, Spain. alberto.carmonabayonas@gmail.com.

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.

No MeSH data available.


Related in: MedlinePlus

The competition between tumor subclones for the resources provided by neoangiogenesis, classifies cells in angiogenic winners and losers. Distant interactions are the result of the extension of local pressures.
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f4-cancers-03-00945: The competition between tumor subclones for the resources provided by neoangiogenesis, classifies cells in angiogenic winners and losers. Distant interactions are the result of the extension of local pressures.

Mentions: This is a compelling clue that suggests that EMT is the preferred cell program in certain conditions such as: (1) when neangiogenesis is not sufficient; (2) or when it is strongly blocked by endogenous inhibitors or by drugs; (3) or when the tumor vasculature is harshly disrupted [48], and also (4) as Brabletz et al. proved, in the periphery of the tumor, where cells receive stromal cues directly. In these situations, cancer cells seek the alternative mechanism to angiogenesis, which involves invasion [49,50]. Interestingly, this behavior has been checked in the clinical setting, in which antiangiogenics appear to promote multicentric patterns of progression [51]. If we now return to the ecological paradigm, it is appealing to envision a model in which the subclones can be divided into angiogenic winners and losers (Figure 4). The former ones would tend to remain encapsulated or microinvasive, and the losers would form large fronts of invasion that constitute the basis of metastasis. Paez-Ribes has recently demonstrated that VEGFR2 blockade is linked to a higher dissemination and tendency to metastasize in a transgenic mouse model [52]. Notably, in this experience, lymph-node metastases were 4-fold higher in treated animals than in controls, and liver metastases were 2-fold higher, and very interestingly, the invasive cells were also able to invade the adjacent microvasculature as expected. The development of evasive resistance to drugs may involve the same mechanism. Elbos et al. [53] have reported an accelerated metastatic tumor growth in mice models treated with the VEGFR/PDGFR inhibitor sunitinib, even though this treatment is effective in vitro. This observation is outstandingly reminiscent of some recent clinical research results. Both bevacizumab and cetuximab are successful in treating metastatic colorectal cancer. Taking into account that VEGF and EGF pathways are connected, the dual inhibition was supposed to be an attractive strategy. In fact, preclinical studies had shown the synergy between anti-EGFR and antiangiogenic therapy. Two recent randomized clinical trials notably apply this notion, the PACCE and Cairo-2 trials, failed to confirm this preclinical assumption. In fact, the dual inhibition yielded a poorer result, worsening the PFS of the whole population [54,55].


An evolutionary explanation for the perturbation of the dynamics of metastatic tumors induced by surgery and acute inflammation.

Carmona Bayonas A - Cancers (Basel) (2011)

The competition between tumor subclones for the resources provided by neoangiogenesis, classifies cells in angiogenic winners and losers. Distant interactions are the result of the extension of local pressures.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756398&req=5

f4-cancers-03-00945: The competition between tumor subclones for the resources provided by neoangiogenesis, classifies cells in angiogenic winners and losers. Distant interactions are the result of the extension of local pressures.
Mentions: This is a compelling clue that suggests that EMT is the preferred cell program in certain conditions such as: (1) when neangiogenesis is not sufficient; (2) or when it is strongly blocked by endogenous inhibitors or by drugs; (3) or when the tumor vasculature is harshly disrupted [48], and also (4) as Brabletz et al. proved, in the periphery of the tumor, where cells receive stromal cues directly. In these situations, cancer cells seek the alternative mechanism to angiogenesis, which involves invasion [49,50]. Interestingly, this behavior has been checked in the clinical setting, in which antiangiogenics appear to promote multicentric patterns of progression [51]. If we now return to the ecological paradigm, it is appealing to envision a model in which the subclones can be divided into angiogenic winners and losers (Figure 4). The former ones would tend to remain encapsulated or microinvasive, and the losers would form large fronts of invasion that constitute the basis of metastasis. Paez-Ribes has recently demonstrated that VEGFR2 blockade is linked to a higher dissemination and tendency to metastasize in a transgenic mouse model [52]. Notably, in this experience, lymph-node metastases were 4-fold higher in treated animals than in controls, and liver metastases were 2-fold higher, and very interestingly, the invasive cells were also able to invade the adjacent microvasculature as expected. The development of evasive resistance to drugs may involve the same mechanism. Elbos et al. [53] have reported an accelerated metastatic tumor growth in mice models treated with the VEGFR/PDGFR inhibitor sunitinib, even though this treatment is effective in vitro. This observation is outstandingly reminiscent of some recent clinical research results. Both bevacizumab and cetuximab are successful in treating metastatic colorectal cancer. Taking into account that VEGF and EGF pathways are connected, the dual inhibition was supposed to be an attractive strategy. In fact, preclinical studies had shown the synergy between anti-EGFR and antiangiogenic therapy. Two recent randomized clinical trials notably apply this notion, the PACCE and Cairo-2 trials, failed to confirm this preclinical assumption. In fact, the dual inhibition yielded a poorer result, worsening the PFS of the whole population [54,55].

Bottom Line: The postsurgical patterns of progression include unexpected features such as distant interactions and variable rhythms.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology and Medical Oncology, Hospital Morales Meseguer, Murcia, Spain. alberto.carmonabayonas@gmail.com.

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.

No MeSH data available.


Related in: MedlinePlus