2.50
Hdl Handle:
http://hdl.handle.net/10541/96922
Title:
Apoptosis and cancer chemotherapy.
Authors:
Hickman, John A; Potten, Christopher S; Merritt, A J; Fisher, T C
Abstract:
The major disseminated cancers remain stubbornly resistant to systemic therapy. Drug-resistant tumours include both slow and fast growing types, with the carcinomas constituting the major problem. Strategies for drug discovery have, in the past, been focused on attempts to design antiproliferative agents, largely targeted to interfere with DNA integrity and replication. The malignant phenotype might be characterized by the emergence of cell populations with a greater survival potential: a lower proclivity to undergo apoptosis. This idea provides a possible explanation of the genesis and progression of cancer and of the inherent resistance of tumour cells to engage apoptosis. Work is described which identifies the molecular basis for differences in the survival potential of stem cells in the crypts of the colon and small intestine. The advantageous survival of colonic stem cells, provided by expression of bcl-2 and a muted p53 response to DNA damage, allows damaged cells to survive. Continued expression of bcl-2 renders tumour cells resistant to drug-induced DNA damage by a mechanism different from classical mechanisms of drug resistance. The attenuation of cell survival is described as a key component in strategies for the drug treatment of disseminated cancers.
Affiliation:
Cancer Research Campaign Molecular and Cellular Pharmacology Group, School of Biological Sciences, University of Manchester, U.K.
Citation:
Apoptosis and cancer chemotherapy. 1994, 345 (1313):319-25 Philos. Trans. R. Soc. Lond., B, Biol. Sci.
Journal:
Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Issue Date:
30-Aug-1994
URI:
http://hdl.handle.net/10541/96922
DOI:
10.1098/rstb.1994.0112
PubMed ID:
7846129
Type:
Article
Language:
en
ISSN:
0962-8436
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorHickman, John Aen
dc.contributor.authorPotten, Christopher Sen
dc.contributor.authorMerritt, A Jen
dc.contributor.authorFisher, T Cen
dc.date.accessioned2010-04-20T16:01:28Z-
dc.date.available2010-04-20T16:01:28Z-
dc.date.issued1994-08-30-
dc.identifier.citationApoptosis and cancer chemotherapy. 1994, 345 (1313):319-25 Philos. Trans. R. Soc. Lond., B, Biol. Sci.en
dc.identifier.issn0962-8436-
dc.identifier.pmid7846129-
dc.identifier.doi10.1098/rstb.1994.0112-
dc.identifier.urihttp://hdl.handle.net/10541/96922-
dc.description.abstractThe major disseminated cancers remain stubbornly resistant to systemic therapy. Drug-resistant tumours include both slow and fast growing types, with the carcinomas constituting the major problem. Strategies for drug discovery have, in the past, been focused on attempts to design antiproliferative agents, largely targeted to interfere with DNA integrity and replication. The malignant phenotype might be characterized by the emergence of cell populations with a greater survival potential: a lower proclivity to undergo apoptosis. This idea provides a possible explanation of the genesis and progression of cancer and of the inherent resistance of tumour cells to engage apoptosis. Work is described which identifies the molecular basis for differences in the survival potential of stem cells in the crypts of the colon and small intestine. The advantageous survival of colonic stem cells, provided by expression of bcl-2 and a muted p53 response to DNA damage, allows damaged cells to survive. Continued expression of bcl-2 renders tumour cells resistant to drug-induced DNA damage by a mechanism different from classical mechanisms of drug resistance. The attenuation of cell survival is described as a key component in strategies for the drug treatment of disseminated cancers.en
dc.language.isoenen
dc.subjectColonic Canceren
dc.subjectCanceren
dc.subject.meshAnimals-
dc.subject.meshApoptosis-
dc.subject.meshColonic Neoplasms-
dc.subject.meshDrug Resistance-
dc.subject.meshGene Expression-
dc.subject.meshGenes, p53-
dc.subject.meshHumans-
dc.subject.meshNeoplasms-
dc.subject.meshProto-Oncogene Proteins-
dc.subject.meshProto-Oncogene Proteins c-bcl-2-
dc.titleApoptosis and cancer chemotherapy.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Molecular and Cellular Pharmacology Group, School of Biological Sciences, University of Manchester, U.K.en
dc.identifier.journalPhilosophical Transactions of the Royal Society of London. Series B, Biological Sciencesen

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