Molekulare Mechanismen der Chemoresistenz und Möglichkeiten der Überwindung

Zusammenfassung

Aufgrund der multiplen zugrunde liegenden genetischen Veränderungen stellt das Mammakarzinom eine nur partiell chemosensitive Erkrankung dar. Diese Veränderungen betreffen in erster Linie Zellzyklusregulation (z. B. über p53-Funktion), Apoptose, DNA-Reparaturmechanismen, Tumor-Stroma-Interaktionen und Transportmechanismen der Zelle. Die Chemoresistenz kann primärer intrinsischer Natur sein, was z. B. bei Stammzellen diskutiert wird, oder sich sekundär extrinsisch ausbilden, was im Verlauf der Therapie auf verschiedenen Wegen entstehen kann. Bislang haben Daten zu Resistenzmechanismen wenig Eingang in die Planung von Chemotherapieregimes gefunden, mit zunehmender Kenntnis molekularer Tumorprofile und molekularer Zielstrukturen für die herkömmlichen Chemotherapieregimes könnte sich dies jedoch ändern.

Abstract

Due to its numerous genetic aberrations, breast cancer is an only partially chemosensitive disease. These genetic changes predominantly affect cell cycle regulation (e.g., via the p53 function), apoptosis, DNA repair mechanisms, tumor-stroma interactions, and the drug transport activities of the tumor cell. Chemoresistance can be of a primary/intrinsic nature, as is currently being discussed for tumor stem cells, or of a secondary/extrinsic nature, emerging, for example, during chemotherapeutic treatment or disease progression. So far, data on chemoresistance has only gradually begun to influence clinical management and the design of chemotherapy regimens. This is likely to change in the near future due to the increased knowledge of tumor profiling and molecular target structures.

Schlüsselwörter

Brustkrebs - prognostischer Marker - Medikamentenresistenz - Chemotherapie

Key words

breast cancer - predictive markers - drug resistance - chemotherapy

Literatur

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