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Critical Reviews™ in Oncogenesis
SJR: 0.631 SNIP: 0.503 CiteScore™: 2.2

ISSN Print: 0893-9675
ISSN Online: 2162-6448

Critical Reviews™ in Oncogenesis

DOI: 10.1615/CritRevOncog.2016016987
pages 253-267

Cell Death Induction in Cancer Therapy − Past, Present, and Future

Lisa Nonnenmacher
Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
Sebastian Hasslacher
Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
Julia Zimmermann
Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
Georg Karpel-Massler
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, U.S.A.; Department of Neurosurgery, University Medical Center Ulm, Ulm, Germany
Katia La Ferla-Brühl
Laboratorio Analisi Sicilia Catania, Lentini; SR, Italy
Sara E. Barry
School of Built and Natural Environment, Glasgow Caledonian University, Glasgow, Scotland
Timo Burster
Department of Neurosurgery, University Medical Center Ulm, Ulm, Germany
Markus D. Siegelin
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, U.S.A.
Oliver Brühl
Laboratorio Analisi Sicilia Catania, Lentini; SR, Italy
Marc-Eric Halatsch
Department of Neurosurgery, University Medical Center Ulm, Ulm, Germany
Klaus-Michael Debatin
Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
Mike-Andrew Westhoff
Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany

ABSTRACT

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.


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