Screening for modulators of cisplatin sensitivity: Unbiased screens reveal common themes

Cisplatin is a widely used chemotherapeutic agent to treat a variety of solid tumors. The cytotoxic mode of action of cisplatin is mediated by inducing conformational changes in DNA including intra- and inter-strand crosslink adducts. Recognition of these adducts results in the activation of the DNA...

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Published in:Cell cycle (Georgetown, Tex.) Vol. 10; no. 3; pp. 380 - 386
Main Authors: Nijwening, Jeroen H., Kuiken, Hendrik J., Beijersbergen, Roderick L.
Format: Journal Article
Language:English
Published: United States Taylor & Francis 01.02.2011
Subjects:
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Apoptosis - physiology
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cisplatin - pharmacology
Cycle
DNA Adducts - drug effects
DNA Repair
Drug Resistance, Neoplasm - genetics
Humans
Landes
Organogenesis
Proteins
Saccharomyces cerevisiae - drug effects
Saccharomyces cerevisiae - genetics
ISSN:1538-4101, 1551-4005, 1551-4005
Online Access:Get full text
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Summary:Cisplatin is a widely used chemotherapeutic agent to treat a variety of solid tumors. The cytotoxic mode of action of cisplatin is mediated by inducing conformational changes in DNA including intra- and inter-strand crosslink adducts. Recognition of these adducts results in the activation of the DNA damage response resulting in cell cycle arrest, repair, and potentially, apoptosis. Despite the clinical efficacy of cisplatin, many tumors are either intrinsically resistant or acquire resistance during treatment. The identification of cisplatin drug response modulators can help us understand these resistance mechanisms, provide biomarkers for treatment strategies, or provide drug targets for combination therapy. Here we discuss functional genetic screens, including one performed by us, set up to identify genes whose inhibition results in increased sensitivity to cisplatin. In summary, the validated genes identified in these screens mainly operate in DNA damage response including nucleotide excision repair, translesion synthesis, and homologous recombination.
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ISSN:1538-4101
1551-4005
1551-4005
DOI:10.4161/cc.10.3.14642