Populations of tumor cells show remarkable variability in almost every discernable phenotypic trait, including clinically important phenotypes such as ability to seed metastases and to survive therapy. Cancer evolution following Darwinian logic assumes that only the genetically “fittest” clone survives. This may not necessary be true as several lines of evidence argue that tumor growth most closely resembles evolution in an expanding population, such as that the most advantageous mutations are not always selected to fixation. Instead, we can envisage a situation in which several cancer sub-clones exist, each with non-identical mutation complement and hence different rates of clonal expansion. Clones are “born”, expand, contract and “die” through tumorigenesis. As the microenvironment changes (e.g. after application of a drug), different mutations become more of less favorable, perhaps causing bottleneck at which only the most “fittest” survive. Such a model clearly implies that tumors are, at some level, polyclonal.
In this model, the cancer that clinically presents is still derived from a single originating cell. However, the evolution of the tumor is more complex, with genetically divergent tumor clones co-existing within tumors for substantial periods of time. Cancer polyclonality at such scale and branching evolution has already been shown (although only for single cases so far) for early as well as advanced stages of several solid tumors.
This Research Topic aims to present novel insights on molecular mechanisms as well as the diagnostic and prognostic implications of intra-tumor heterogeneity in different cancer subtypes, and on its predictive relevance, as related to responsiveness and resistance to targeted drugs and chemotherapy.
Populations of tumor cells show remarkable variability in almost every discernable phenotypic trait, including clinically important phenotypes such as ability to seed metastases and to survive therapy. Cancer evolution following Darwinian logic assumes that only the genetically “fittest” clone survives. This may not necessary be true as several lines of evidence argue that tumor growth most closely resembles evolution in an expanding population, such as that the most advantageous mutations are not always selected to fixation. Instead, we can envisage a situation in which several cancer sub-clones exist, each with non-identical mutation complement and hence different rates of clonal expansion. Clones are “born”, expand, contract and “die” through tumorigenesis. As the microenvironment changes (e.g. after application of a drug), different mutations become more of less favorable, perhaps causing bottleneck at which only the most “fittest” survive. Such a model clearly implies that tumors are, at some level, polyclonal.
In this model, the cancer that clinically presents is still derived from a single originating cell. However, the evolution of the tumor is more complex, with genetically divergent tumor clones co-existing within tumors for substantial periods of time. Cancer polyclonality at such scale and branching evolution has already been shown (although only for single cases so far) for early as well as advanced stages of several solid tumors.
This Research Topic aims to present novel insights on molecular mechanisms as well as the diagnostic and prognostic implications of intra-tumor heterogeneity in different cancer subtypes, and on its predictive relevance, as related to responsiveness and resistance to targeted drugs and chemotherapy.
