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Unblinding the watchmaker: cancer treatment and drug design in the face of evolutionary pressure.
Konig, Sophia; Strobel, Hannah; Grunert, Michael; Lyszkiewicz, Marcin; Brühl, Oliver; Karpel-Massler, Georg; Zietara, Natalia; La Ferla-Brühl, Katia; Siegelin, Markus D; Debatin, Klaus-Michael; Westhoff, Mike-Andrew.
Afiliación
  • Konig S; Department of Pediatrics and Adolescent Medicine, Ulm University Hospital, Ulm, Germany.
  • Strobel H; Department of Pediatrics and Adolescent Medicine, Ulm University Hospital, Ulm, Germany.
  • Grunert M; Department of Nuclear Medicine, German Armed Forces Hospital of Ulm, Ulm, Germany.
  • Lyszkiewicz M; Department of Pediatrics and Adolescent Medicine, Ulm University Hospital, Ulm, Germany.
  • Brühl O; Laboratorio Analisi Sicilia, Catania, Lentini, Italy.
  • Karpel-Massler G; Department of Neurosurgery, Ulm University Hospital, Ulm, Germany.
  • Zietara N; Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharma GmbH & Co. KG, Germany.
  • La Ferla-Brühl K; Laboratorio Analisi Sicilia, Catania, Lentini, Italy.
  • Siegelin MD; Department of Pathology and Cell Biology, Columbia University Medical Center, Albany, NY, USA.
  • Debatin KM; Department of Pediatrics and Adolescent Medicine, Ulm University Hospital, Ulm, Germany.
  • Westhoff MA; Department of Pediatrics and Adolescent Medicine, Ulm University Hospital, Ulm, Germany.
Expert Opin Drug Discov ; 17(10): 1081-1094, 2022 10.
Article en En | MEDLINE | ID: mdl-35997138
ABSTRACT

INTRODUCTION:

Death due to cancer is mostly associated with therapy ineffectiveness, i.e. tumor cells no longer responding to treatment. The underlying dynamics that facilitate this mutational escape from selective pressure are well studied in several other fields and several interesting approaches exist to combat this phenomenon, for example in the context of antibiotic-resistance in bacteria. AREAS COVERED Ninety percent of all cancer-related deaths are associated with treatment failure. Here, we discuss the common treatment modalities and prior attempts to overcome acquired resistance to therapy. The underlying molecular mechanisms are discussed and the implications of emerging resistance in other systems, such as bacteria, are discussed in the context of cancer. EXPERT OPINION Reevaluating emerging therapy resistance in tumors as an evolutionary mechanism to survive in a rapidly and drastically altering fitness landscape leads to novel treatment strategies and distinct requirements for new drugs. Here, we propose a scheme of considerations that need to be applied prior to the discovery of novel therapeutic drugs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diseño de Fármacos / Neoplasias Límite: Humans Idioma: En Revista: Expert Opin Drug Discov Año: 2022 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diseño de Fármacos / Neoplasias Límite: Humans Idioma: En Revista: Expert Opin Drug Discov Año: 2022 Tipo del documento: Article País de afiliación: Alemania