MMS19 as a potential predictive marker of adjuvant chemotherapy benefit in resected non-small cell lung cancer

MMS19 作为切除的非小细胞肺癌辅助化疗益处的潜在预测标志物

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作者:Julien Adam, Tony Sourisseau, Ken A Olaussen, Angélique Robin, Chang Q Zhu, Alexandre Templier, Alexandre Civet, Philippe Girard, Vladimir Lazar, Pierre Validire, Ming S Tsao, Jean-Charles Soria, Benjamin Besse

Background

Resectable non-small cell lung cancer (NSCLC) treatment options most often consist of surgical resection along with adjuvant chemotherapy (ACT). The benefit of ACT however is modest and is accompanied by important side effects.

Conclusions

We therefore propose the expression level of MMS19 as a candidate predictive marker of ACT benefit in resected NSCLC patients.

Methods

We applied an unbiased approach based on high content analysis of expression data generated from a discovery patient cohort.

Objective

One central quest in the field is therefore the identification of a predictive marker of the response to ACT.

Results

We identified MMS19, a component of the cytoplasmic Iron-Sulfur Assembly (CIA) machinery important for the Nucleotide Excision Repair (NER) pathway as a pivotal gene for cisplatin toxicity. We then confirmed the association between MMS19 expression and the response to Cisplatin treatment in a panel of NSCLC cell lines. Finally we validated these pre-clinical data in a subgroup of JBR.10 trial patients through a hypothesis-driven analysis, and showed that MMS19 levels associated with ACT benefit. Conclusions: We therefore propose the expression level of MMS19 as a candidate predictive marker of ACT benefit in resected NSCLC patients.

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