title: Novel Approaches to Apoptosis-Inducing Therapies.
abstract: Induction of apoptotic programmed cell death is one of the underlying principles of most current cancer therapies. In this review, we discuss the limitations and drawbacks of this approach and identify three distinct, but overlapping strategies to avoid these difficulties and further enhance the efficacy of apoptosis-inducing therapies. We postulate that the application of multi-targeted small molecule inhibitor cocktails will reduce the risk of the cancer cell populations developing resistance towards therapy. Following from these considerations regarding population genetics and ecology, we advocate the reconsideration of therapeutic end points to maximise the benefits, in terms of quantity and quality of life, for the patients. Finally, combining both previous points, we also suggest an altered focus on the cellular and molecular targets of therapy, i.e. targeting the (cancer cells') interaction with the tumour microenvironment.
authors: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Eythstrasse 24, 89075, Ulm, Germany.
authors: Mike-Andrew
authors: MA
authors: Westhoff
authors: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Eythstrasse 24, 89075, Ulm, Germany.
authors: Nicolas
authors: N
authors: Marschall
authors: Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Eythstrasse 24, 89075, Ulm, Germany. klaus-michael.debatin@uniklinik-ulm.de.
authors: Klaus-Michael
authors: KM
authors: Debatin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D004334:Drug Administration Schedule; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000502:physiology; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D035703:Therapies, Investigational; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: Adaptive therapy; Bcl-2 family; Combination therapy; ERK signalling; IAPs; Inducer & sensitiser; Intratumour heterogeneity; Microenvironment; PI3K signalling