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Targeting cancer's weaknesses (not its strengths): Therapeutic strategies suggested by the atavistic model
Author(s) -
Lineweaver Charles H.,
Davies Paul C. W.,
Vincent Mark D.
Publication year - 2014
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.201400070
Subject(s) - cancer , weakness , biology , immune system , immunity , cancer cell , mechanism (biology) , acquired immune system , strengths and weaknesses , tumor progression , cancer research , neuroscience , immunology , psychology , genetics , anatomy , social psychology , philosophy , epistemology
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. Also watch the Video Abstract .