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A short update on cancer chemoresistance

Chemoresistenz bei Tumorerkrankungen – eine aktuelle Übersicht

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Summary

Chemotherapeutic interventions in cancer patients are limited by the appearance of chemoresistance. For instance, advanced lung and ovarian cancer patients relapse invariably after few cycles of platinum-based chemotherapy. Disseminated tumors are characterized by genetic instability/heterogeneity, thus containing or generating a repertoire of resistant subpopulations. At the cellular level, altered drug uptake, efflux, and metabolization, as well as modifications of drug targets, increased repair, and decreased cell death complement the limited perfusion and adverse hypoxic/acidic extracellular conditions at the tumor level in retaining cancer cell viability. Similarly, targeted therapy is rendered ineffective by mutations of the specific target protein within a few months or years of administration. Assessment of the expression profiles of resistant tumor cells revealed extensive changes in numerous pathways affecting hundreds of genes. Therefore, reversal of drug resistance will require individual profiles of drug resistance mediators and the combination of several specific drugs, targeting critical components to provide new therapeutic options.

Zusammenfassung

Die Chemotherapie wird in Krebspatienten durch das Auftreten von Chemoresistenz begrenzt. Zum Beispiel rezidivieren Lungen- und Ovarialkarzinompatienten schon nach wenigen Zyklen der platinbasierten Chemotherapie. Disseminierte Tumoren weisen genetische Instabilität/Heterogenität auf und enthalten oder generieren resistente Subpopulationen. Auf der Zellebene komplementieren veränderte Wirkstoffaufnahme, -efflux und –metabolisierung, Modifikationen der Zielproteine, gesteigerte Reparaturprozesse und verminderter Zelltod die herabgesetzte Perfusion und die ungünstigen hypoxischen/azidotischen Bedingungen auf Tumorebene, die die Viabilität der Tumorzellen erhalten. In ähnlicher Weise wird bei der zielgerichteten Chemotherapie die Wirksamkeit durch Mutationen des Zielproteins innerhalb weniger Monate oder Jahre herabgesetzt. Eine Erfassung der Expressionsprofile resistenter Tumorzellen zeigen Änderungen in zahlreichen Stoffwechselwegen die hunderte Gene betreffen. Folglich verlangt die erfolgreiche Reversion der Resistenz die Erfassung individueller Profile der verantwortlichen Mediatoren und den Einsatz einer Kombination von Wirkstoffen gegen kritische Zielproteine.

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  1. Ludwig Boltzmann Cluster of Translational Oncology, c/o Balderichgasse 26/13, 11170, Vienna, Austria

    Gerhard Hamilton & Barbara Rath

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  1. Gerhard Hamilton
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Correspondence to Gerhard Hamilton.

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Hamilton, G., Rath, B. A short update on cancer chemoresistance. Wien Med Wochenschr 164, 456–460 (2014). https://doi.org/10.1007/s10354-014-0311-z

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  • DOI: https://doi.org/10.1007/s10354-014-0311-z

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