Cellular Heterogeneity and Molecular Evolution in Cancer

Almendro, Vanessa; Marusyk, Andriy; Polyák, Kornélia

doi:10.1146/annurev-pathol-020712-163923

Cited by 440 publications

(413 citation statements)

References 150 publications

(170 reference statements)

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“…Intra-tumor heterogeneity, the coexistence of different clones within a tumor, is commonly observed [Greenman et al 2007, Navin et al 2011 and has implications for cancer progression, diagnosis, and treatment [Dexter & Leith 1986, Maley et al 2006, Almendro et al 2013]. Why such heterogeneity exists remains unclear [Merlo et al 2006, Almendro et al 2013, because clones that have a proliferative advantage within the tumour are expected to drive other subclones to extinction.…”

Section: Implications For Cancer Researchmentioning

confidence: 99%

“…Why such heterogeneity exists remains unclear [Merlo et al 2006, Almendro et al 2013, because clones that have a proliferative advantage within the tumour are expected to drive other subclones to extinction. In the light of evolutionary game theory, however, stable intra-tumor heterogeneity is easily explained as a stable polymorphic equilibrium resulting from the non-linear benefit of growth factors [Archetti et al 2015].…”

Section: Implications For Cancer Researchmentioning

confidence: 99%

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Cooperation among cancer cells as public goods games on Voronoi networks

Archetti

2016

Journal of Theoretical Biology

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Cancer cells produce growth factors that diffuse and sustain tumor proliferation, a form of cooperation among cancer cells that can be studied using mathematical models of public goods in the framework of evolutionary game theory. Cell populations, however, form heterogeneous networks that cannot be described by regular lattices or scale-free networks, the types of graphs generally used in the study of cooperation. To describe the dynamics of growth factor production in populations of cancer cells, I study public goods games on Voronoi networks, using a range of non-linear benefits that account for the known properties of growth factors, and different types of diffusion gradients. The results are surprisingly similar to those obtained on regular graphs and different from results on scale-free networks, revealing that network heterogeneity per se does not promote cooperation when public goods diffuse beyond one-step neighbours. The exact shape of the diffusion gradient is not crucial, however, whereas the type of non-linear benefit is an essential determinant of the dynamics. Public goods games on Voronoi networks can shed light on intra-tumor heterogeneity, the evolution of resistance to therapies that target growth factors, and new types of cell therapy.

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Section: Implications For Cancer Researchmentioning

confidence: 99%

Section: Implications For Cancer Researchmentioning

confidence: 99%

Cooperation among cancer cells as public goods games on Voronoi networks

Archetti

2016

Journal of Theoretical Biology

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“…Tumor cells constantly undergo clonal selection as a result of genetic and epigenetic changes, a process culminating with the presence of distinct subpopulations within the bulk of tumor. 121,122 The clonal composition of a tumor will change depending on the various stages of tumor propagation, hence those mutations that enhance cell division will be selected during the early tumor stage for rapid mass growth, whereas others permitting increased invasiveness and chemoresistance during the later stages. 123 Recent discoveries have shown that RMS tumors seem to be composed of a dominant clone, although each tumor contains subclonal populations with a unique mutational profile, which may provide selective advantage to a relapse or metastatic tumor.…”

Section: Targeting Intratumor Cell Heterogeneity: a Difficult But Promentioning

confidence: 99%

Uncovering metabolism in rhabdomyosarcoma

Monti

Fanzani

2016

Cell Cycle

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Rhabdomyosarcoma (RMS) is a myogenic tumor classified as the most frequent soft tissue sarcoma affecting children and adolescents. The histopathological classification includes five different histotypes, with two most predominant referred as to embryonal and alveolar, the latter being characterized by adverse outcome. The current molecular classification identifies two major subsets, those harboring the fused Pax3-Foxo1 transcription factor generating from a recurrent specific translocation (fusion-positive RMS), and those lacking this signature but harboring mutations in the RAS/PI3K/AKT signalling axis (fusion-negative RMS). Since little attention has been devoted to RMS metabolism until now, in this review we summarize the “state of art” of metabolism and discuss how some of the molecular signatures found in this cancer, as observed in other more common tumors, can predict important metabolic challenges underlying continuous cell growth, oxidative stress resistance and metastasis, which could be the subject of future targeted therapies

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“…The role of the tumor microenvironment including extracellular matrix components and soluble factors in tumor progression [30] and drug resistance [31]has been gradually recognized. Among these factors, abnormal autocrine/paracrine signaling has been associated with breast tumor progression [32].…”

Section: Discussionmentioning

confidence: 99%

Oncogenic transformation of normal breast epithelial cells co-cultured with cancer cells

Song

Zhou

et al. 2018

Cell Cycle

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The heterogeneity in human breast cancer poses a challenge for effective treatment. Better understanding of tumor initiation and development will help to resolve this problem. Current models explaining intratumoral diversity include cancer stem cells, clonal evolution and cancer cell dedifferentiation and reprogramming. Herein, a new model, cancer transmission, is proposed to explain cancer heterogeneity. We found breast cancer cells (MCF10A.NeuT) were capable of transforming normal mammary epithelial cells (MCF10A). The transformed cells exhibited cancerous properties including enhanced proliferation and migration, loss of apical-basal polarity and depolarized acini structure associated with epithelial-mesenchymal transition (EMT). The transformed MCF10A cells displayed distinct EMT characteristics compared to parental cells. We further showed that cancer cell-secreted factors were sufficient to induce cancerous transformation of normal cells. Furthermore, transformed cells were resistant to radiation treatment, providing new insights into mechanisms underlying therapeutic resistance.

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Cellular Heterogeneity and Molecular Evolution in Cancer

Cited by 440 publications

References 150 publications

Cooperation among cancer cells as public goods games on Voronoi networks

Cooperation among cancer cells as public goods games on Voronoi networks

Uncovering metabolism in rhabdomyosarcoma

Oncogenic transformation of normal breast epithelial cells co-cultured with cancer cells

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