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Evolving concepts of tumor heterogeneity.

Zellmer VR, Zhang S - Cell Biosci (2014)

Bottom Line: This evolutionary model of tumorigenesis has largely been shaped by seminal reports of fitness-promoting mutations conferring a malignant cellular phenotype.Despite the major clinical and intellectual advances that have resulted from studying heritable heterogeneity, it has long been overlooked that compositional tumor heterogeneity and tumor microenvironment (TME)-induced selection pressures drive tumor evolution, significantly contributing to tumor development and outcomes of clinical cancer treatment.In this review, we seek to summarize major milestones in tumor evolution, identify key aspects of tumor heterogeneity in a TME-dependent evolutionary context, and provide insights on the clinical challenges facing researchers and clinicians alike.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Science, Harper Cancer Research Institute, University of Notre Dame, A130 Harper Hall, Notre Dame, IN 46556 USA.

ABSTRACT
Past and recent findings on tumor heterogeneity have led clinicians and researchers to broadly define cancer development as an evolving process. This evolutionary model of tumorigenesis has largely been shaped by seminal reports of fitness-promoting mutations conferring a malignant cellular phenotype. Despite the major clinical and intellectual advances that have resulted from studying heritable heterogeneity, it has long been overlooked that compositional tumor heterogeneity and tumor microenvironment (TME)-induced selection pressures drive tumor evolution, significantly contributing to tumor development and outcomes of clinical cancer treatment. In this review, we seek to summarize major milestones in tumor evolution, identify key aspects of tumor heterogeneity in a TME-dependent evolutionary context, and provide insights on the clinical challenges facing researchers and clinicians alike.

No MeSH data available.


Related in: MedlinePlus

Timeline of the evolving concepts of tumor heterogeneity.
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Fig1: Timeline of the evolving concepts of tumor heterogeneity.

Mentions: All tumors possess some form of somatic mutation, and our current understanding of tumor heterogeneity is built upon the principle that acquired mutations are heritable [11]. Essential to this point is Theodor Boveri’s keen observation at the beginning of the twentieth century that aberrant mitoses are associated with malignant tumors and his findings on inheritance factors [12]. Boveri traced the fate of each cell and found that cells with different chromosome combinations were phenotypically dissimilar, which led to two main conclusions: (1) chromosomes transmit different inheritance factors and (2) unequal chromosome distribution is detrimental to normal development [13]. Decades later, key reports by David Hungerford, Peter Nowell, and Janet Rowley further substantiated Boveri’s hypothesis, becoming one of the most important milestones in cancer research [14, 15]. In 1976, Nowell published a now infamous paper depicting a working model for tumor evolution [5]. Among several persuasive thoughts, Nowell described a cancer progression model where major genetic errors drive natural selection of cells with improved fitness in response to intrinsic and extrinsic pressures. This ecological view of tumor development has captivated researchers and become a core concept in today’s cancer research (Figure 1).Figure 1


Evolving concepts of tumor heterogeneity.

Zellmer VR, Zhang S - Cell Biosci (2014)

Timeline of the evolving concepts of tumor heterogeneity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4417538&req=5

Fig1: Timeline of the evolving concepts of tumor heterogeneity.
Mentions: All tumors possess some form of somatic mutation, and our current understanding of tumor heterogeneity is built upon the principle that acquired mutations are heritable [11]. Essential to this point is Theodor Boveri’s keen observation at the beginning of the twentieth century that aberrant mitoses are associated with malignant tumors and his findings on inheritance factors [12]. Boveri traced the fate of each cell and found that cells with different chromosome combinations were phenotypically dissimilar, which led to two main conclusions: (1) chromosomes transmit different inheritance factors and (2) unequal chromosome distribution is detrimental to normal development [13]. Decades later, key reports by David Hungerford, Peter Nowell, and Janet Rowley further substantiated Boveri’s hypothesis, becoming one of the most important milestones in cancer research [14, 15]. In 1976, Nowell published a now infamous paper depicting a working model for tumor evolution [5]. Among several persuasive thoughts, Nowell described a cancer progression model where major genetic errors drive natural selection of cells with improved fitness in response to intrinsic and extrinsic pressures. This ecological view of tumor development has captivated researchers and become a core concept in today’s cancer research (Figure 1).Figure 1

Bottom Line: This evolutionary model of tumorigenesis has largely been shaped by seminal reports of fitness-promoting mutations conferring a malignant cellular phenotype.Despite the major clinical and intellectual advances that have resulted from studying heritable heterogeneity, it has long been overlooked that compositional tumor heterogeneity and tumor microenvironment (TME)-induced selection pressures drive tumor evolution, significantly contributing to tumor development and outcomes of clinical cancer treatment.In this review, we seek to summarize major milestones in tumor evolution, identify key aspects of tumor heterogeneity in a TME-dependent evolutionary context, and provide insights on the clinical challenges facing researchers and clinicians alike.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Science, Harper Cancer Research Institute, University of Notre Dame, A130 Harper Hall, Notre Dame, IN 46556 USA.

ABSTRACT
Past and recent findings on tumor heterogeneity have led clinicians and researchers to broadly define cancer development as an evolving process. This evolutionary model of tumorigenesis has largely been shaped by seminal reports of fitness-promoting mutations conferring a malignant cellular phenotype. Despite the major clinical and intellectual advances that have resulted from studying heritable heterogeneity, it has long been overlooked that compositional tumor heterogeneity and tumor microenvironment (TME)-induced selection pressures drive tumor evolution, significantly contributing to tumor development and outcomes of clinical cancer treatment. In this review, we seek to summarize major milestones in tumor evolution, identify key aspects of tumor heterogeneity in a TME-dependent evolutionary context, and provide insights on the clinical challenges facing researchers and clinicians alike.

No MeSH data available.


Related in: MedlinePlus