Oncogene-dependent tumor suppression: using the dark side of the force for cancer therapy

Evan, G.I., Christophorou, M., Lawlor, E.A., Ringshausen, I., Prescott, J., Dansen, T., Finch, A., Martins, C. and Murphy, D. (2005) Oncogene-dependent tumor suppression: using the dark side of the force for cancer therapy. Cold Spring Harbor Symposia on Quantitative Biology, 70, pp. 263-273. (doi: 10.1101/sqb.2005.70.054)

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Abstract

Cancers arise by an evolutionary process that involves the protracted acquisition by somatic cells of suites of interlockingmutations that uncouple proliferation, survival, migration, and damage responses from the mechanisms (selective pressures)that normally restrain or restrict them in time and space. The relative rareness of cancer cells within the soma, in the face ofhuge numbers of available cell targets, substantial rates of mutation, and an abundance of proto-oncogenes and tumor suppressorgene targets, indicates that the evolutionary space available to incipient tumor cells is highly restricted. The principalway in which this is achieved is through intrinsic tumor suppression pathways—innate growth arrest and apoptotic programsthat fulfill an essentially analogous functional role to checkpoints in the cell cycle machinery by antagonizing the tumorigenicpotential of oncogenic mutations. Using switchable transgenic and knockin mouse models, it is possible to identify these varioustumor suppressor programs and establish where, when, how, and why they act to forestall neoplasia in each tissue typeand, consequently, how and why their failure leads to cancer.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Murphy, Professor Daniel
Authors: Evan, G.I., Christophorou, M., Lawlor, E.A., Ringshausen, I., Prescott, J., Dansen, T., Finch, A., Martins, C., and Murphy, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cold Spring Harbor Symposia on Quantitative Biology
ISSN:0091-7451
ISSN (Online):1943-4456

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