title: Cell Death Induction in Cancer Therapy - Past, Present, and Future.
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.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Nonnenmacher
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hasslacher
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Zimmermann
authors.affiliation: 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.
authors.forename: Georg
authors.initials: G
authors.lastname: Karpel-Massler
authors.affiliation: Laboratorio Analisi Sicilia Catania, Lentini; SR, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: La Ferla-Brühl
authors.affiliation: Retired, formerly: School of Built and Natural Environment, Glasgow Caledonian University, Glasgow, Scotland.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Barry
authors.affiliation: Department of Neurosurgery, University Medical Center Ulm, Ulm, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Burster
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, U.S.A.
authors.forename: Markus D
authors.initials: MD
authors.lastname: Siegelin
authors.affiliation: Laboratorio Analisi Sicilia Catania, Lentini; SR, Italy.
authors.forename: Oliver
authors.initials: O
authors.lastname: Brühl
authors.affiliation: Department of Neurosurgery, University Medical Center Ulm, Ulm, Germany.
authors.forename: Marc-Eric
authors.initials: ME
authors.lastname: Halatsch
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Klaus-Michael
authors.initials: KM
authors.lastname: Debatin
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
authors.forename: Mike-Andrew
authors.initials: MA
authors.lastname: Westhoff
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D006801:Humans; D000067552:Mutation Accumulation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents