Genetic instability and darwinian selection in tumours

Cahill, Daniel P.; Kinzler, Kenneth W.; Vogelstein, Bert; Lengauer, Christoph

doi:10.1016/s0168-9525(99)01874-0

Cited by 124 publications

(144 citation statements)

References 38 publications

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“…This two-step process of producing aneuploid cells is consistent with that reported by Shi and King who described that chromosome non-disjunction yields tetraploid cells. (34) As aneuploidy and chromosomal instability are characteristic of many cancer cells and are linked to the progressive development of high-grade invasive tumors, (35) Tacc3 may have a direct role in tumorigenesis and progression. The Tacc3 conditional mutant mice generated in this study will provide an excellent opportunity to test this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

TACC3 is required for the proper mitosis of sclerotome mesenchymal cells during formation of the axial skeleton

2007

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Section: Discussionmentioning

confidence: 99%

TACC3 is required for the proper mitosis of sclerotome mesenchymal cells during formation of the axial skeleton

2007

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“…Many genetic and physiological features specific for malignant cells relating to particular gain-offunction or loss-of-function mutations explain this phenomenon. Cancer cells have undergone a minievolution, involving extensive point-mutations as well as larger chromosomal shifts and alterations, termed chromosomal instability, which provides them with selective growth advantages over normal cells [34]. However, while cancer cells may gain many growth-enhancing attributes, they may simultaneously lose critical components of the intracellular defense mechanisms and thus become fertile ground for the replication of many viruses.…”

Section: Molecular Basis For the Selective Permissiveness Of Cancer Cmentioning

confidence: 99%

Oncolytic viruses in cancer therapy

2007

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Oncolytic virotherapy is a promising form of gene therapy for cancer, employing nature's own agents to find and destroy malignant cells. The purpose of this review is to provide an introduction to this very topical field of research and to point out some of the current observations, insights and ideas circulating in the literature. We have strived to acknowledge as many different oncolytic viruses as possible to give a broader picture of targeting cancer using viruses. Some of the newest additions to the panel of oncolytic viruses include the avian adenovirus, foamy virus, myxoma virus, yaba-like disease virus, echovirus type 1, bovine herpesvirus 4, Saimiri virus, feline panleukopenia virus, Sendai virus and the non-human coronaviruses. Although promising, virotherapy still faces many obstacles that need to be addressed, including the emergence of virus-resistant tumor cells.

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“…1) [4]. The new genetic alterations are driven by genetic instability, one of the hallmarks of tumor cells [5]. Only a small proportion of the total mutational burden is related to the process of clonal evolution because most are passenger mutations with no biological relevance [5].…”

Section: Clonal Evolution During Cancer Progressionmentioning

confidence: 99%

“…The new genetic alterations are driven by genetic instability, one of the hallmarks of tumor cells [5]. Only a small proportion of the total mutational burden is related to the process of clonal evolution because most are passenger mutations with no biological relevance [5]. In addition, treatments can alter clonal heterogeneity by selecting for more resistant cells or perturbing the microenvironmental conditions [6].…”

Section: Clonal Evolution During Cancer Progressionmentioning

confidence: 99%

Beyond molecular tumor heterogeneity: protein synthesis takes control

et al. 2018

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One of the daunting challenges facing modern medicine lies in the understanding and treatment of tumor heterogeneity. Most tumors show intra-tumor heterogeneity at both genomic and proteomic levels, with marked impacts on the responses of therapeutic targets. Therapeutic target-related gene expression pathways are affected by hypoxia and cellular stress. However, the finding that targets such as eukaryotic initiation factor (eIF) 4E (and its phosphorylated form, p-eIF4E) are generally homogenously expressed throughout tumors, regardless of the presence of hypoxia or other cellular stress conditions, opens the exciting possibility that malignancies could be treated with therapies that combine targeting of eIF4E phosphorylation with immune checkpoint inhibitors or chemotherapy.

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Genetic instability and darwinian selection in tumours

Cited by 124 publications

References 38 publications

TACC3 is required for the proper mitosis of sclerotome mesenchymal cells during formation of the axial skeleton

TACC3 is required for the proper mitosis of sclerotome mesenchymal cells during formation of the axial skeleton

Oncolytic viruses in cancer therapy

Beyond molecular tumor heterogeneity: protein synthesis takes control

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