Abstract:
:Although much of cancer research relies on Nowell's clonal evolution hypothesis as a conceptual framework, large gaps remain in understanding how tumors develop. The multistage skin cancer model in mice provides continuing insight on fundamental aspects of tumor evolution. In this model, mutation of the oncogene Hras is frequently the initiating event while mutation of the tumor suppressor p53 is a late event, associated with malignant progression. Recent evidence demonstrates that intracellular signaling from the initial Hras mutation leads directly to the activation of p53, creating selective pressure in favor of cells with mutant p53. Thus, selection for subsequent mutations is mechanistically linked to the initial mutation, explaining the preferred order of mutational events observed. Analysis of this model also reveals that a diverse array of signals can selectively impair or enhance clonal expansion of Ras mutant cells into a visible neoplasm. These modifiers can be genetic, physiological, or environmental and are often highly specific to tumor cells. This indicates that tumor cells have an inherent reduced capacity to buffer against perturbations. Reduced buffering may play an important role in both tumor evolution and therapy response and may be a hallmark of cancer cells.
journal_name
Semin Cancer Bioljournal_title
Seminars in cancer biologyauthors
Kemp CJdoi
10.1016/j.semcancer.2005.06.003keywords:
subject
Has Abstractpub_date
2005-12-01 00:00:00pages
460-73issue
6eissn
1044-579Xissn
1096-3650pii
S1044-579X(05)00036-2journal_volume
15pub_type
杂志文章,评审abstract::The processes of intraepithelial migration, intraluminal seeding, and field cancerization as models for initiation, spread, and recurrences of urothelial cell carcinoma (UCC) are reviewed in light of recent molecular investigations. The accumulated molecular data on synchronous and metachronous tumors indicate that th...
journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
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journal_title:Seminars in cancer biology
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journal_title:Seminars in cancer biology
pub_type: 杂志文章,评审
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journal_title:Seminars in cancer biology
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journal_title:Seminars in cancer biology
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journal_title:Seminars in cancer biology
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journal_title:Seminars in cancer biology
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journal_title:Seminars in cancer biology
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journal_title:Seminars in cancer biology
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journal_title:Seminars in cancer biology
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