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Therapeutic Targeting Of Replicative Immortality, Paul Yaswen, Karen L. Mackenzie, W. Nicol Keith, Patricia Hentosh, Francis Rodier, Jiyue Zhu, Gary L. Firestone, Ander Matheu, Amancio Carnero, Alan Bilsland

School of Medical Diagnostics & Translational Sciences Faculty Publications

One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed “senescence,” can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite …