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

Lisa Nonnenmacher, Sebastian Hasslacher, Julia Zimmermann, Georg Karpel-Massler, Katia La Ferla-Brühl, Sara E Barry, Timo Burster, Markus D Siegelin, Oliver Brühl, Marc-Eric Halatsch, Klaus-Michael Debatin, Mike-Andrew Westhoff

Research output: Contribution to journalReview articlepeer-review

11 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)253-267
Number of pages15
JournalCritical Reviews in Oncogenesis
Issue number3-4
Publication statusPublished - 2016
Externally publishedYes


  • Animals
  • Antineoplastic Agents
  • Apoptosis
  • Humans
  • Mutation Accumulation
  • Neoplasms
  • Tumor Microenvironment
  • Journal Article
  • Review


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