RT Journal Article ID 756bfbeb6a585101 A1 Nonnenmacher, Lisa A1 Hasslacher, Sebastian A1 Zimmermann, Julia A1 Karpel-Massler, Georg A1 La Ferla-Brühl, Katia A1 Barry, Sara E. A1 Burster, Timo A1 Siegelin, Markus D. A1 Brühl, Oliver A1 Halatsch, Marc-Eric A1 Debatin, Klaus-Michael A1 Westhoff, Mike-Andrew T1 Cell Death Induction in Cancer Therapy − Past, Present, and Future JF Critical Reviews™ in Oncogenesis JO CRO YR 2016 FD 2016-10-24 VO 21 IS 3-4 SP 253 OP 267 K1 apoptosis K1 cancer therapy K1 Darwinian principles K1 tumor ecosystem K1 therapeutic endpoints AB The induction of apoptosis, a physiological type of cell death, is currently the primary therapeutic aim of most cancer therapies. As resistance to apoptosis is an early hallmark of developing cancer, the success of this treatment strategy is already potentially compromised at treatment initiation. In this review, we discuss the tumor in Darwinian terms and describe it as a complex, yet highly unstable, ecosystem. Current therapeutic strategies often focus on directly killing the dominant subclone within the population of mutated cancer cells while ignoring the subclonal complexity within the ecosystem tumor, the complexity of the direct tumor/ microenvironment interaction and the contribution of the ecosystem human − that is, the global environment which provides the tumor with both support and challenges. The Darwinian view opens new possible therapeutic interventions, such as the disruption of the microenvironment by targeting nonmutated cells within the tumor or the interaction points of mutant tumor cells with their environment, and it forces us to reevaluate therapeutic endpoints. It is our belief that a central future challenge of apoptosis-inducing therapies will be to understand better under which preconditions which treatment strategy and which therapeutic endpoint will lead to the highest quality and quantity of a patient's life. PB Begell House LK https://www.dl.begellhouse.com/journals/439f422d0783386a,5c1116ad47548349,756bfbeb6a585101.html