Insights & Perspectives
Targeting cancer's weaknesses (not its strengths): Therapeutic strategies suggested by the atavistic model
Version of Record online: 14 JUL 2014
© 2014 WILEY Periodicals, Inc.
Volume 36, Issue 9, pages 827–835, September 2014
How to Cite
Lineweaver, C. H., Davies, P. C. W. and Vincent, M. D. (2014), Targeting cancer's weaknesses (not its strengths): Therapeutic strategies suggested by the atavistic model. Bioessays, 36: 827–835. doi: 10.1002/bies.201400070
- Issue online: 13 AUG 2014
- Version of Record online: 14 JUL 2014
- NIH. Grant Number: U54 CA143682
- adaptive immunity;
- cancer therapy;
- evolution of multicellularity
In the atavistic model of cancer progression, tumor cell dedifferentiation is interpreted as a reversion to phylogenetically earlier capabilities. The more recently evolved capabilities are compromised first during cancer progression. This suggests a therapeutic strategy for targeting cancer: design challenges to cancer that can only be met by the recently evolved capabilities no longer functional in cancer cells. We describe several examples of this target-the-weakness strategy. Our most detailed example involves the immune system. The absence of adaptive immunity in immunosuppressed tumor environments is an irreversible weakness of cancer that can be exploited by creating a challenge that only the presence of adaptive immunity can meet. This leaves tumor cells more vulnerable than healthy tissue to pathogenic attack. Such a target-the-weakness therapeutic strategy has broad applications, and contrasts with current therapies that target the main strength of cancer: cell proliferation.
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