Customizing chemotherapy in thoracic malignancies based on ERCC1 expression

Platinum-based chemotherapy regimens using cisplatin or carboplatin are the cornerstones of treatment for advanced non-small-cell lung cancer (NSCLC), smallcell lung cancer and malignant pleural mesothelioma. Despite being standard regimens of choice in the majority of patients without oncogene driver mutations, the activity obtained by individual patients varies considerably. Hence, biomarkers such as ERCC1 are needed to predict sensitivity to drugs, which has been explored as a predictor for platinum sensitivity in thoracic malignancies, mostly in the case of NSCLC. ERCC1 may be measured by mRNA activity; however, most studies have examined protein expression via immunohistochemistry. High ERCC1 expression has been a good prognostic factor in resected NSCLC patients who are not receiving chemotherapy, while it has been an adverse predictor for the effect of cisplatin or carboplatin. The latter has also been shown in malignant pleural mesothelioma. Heterogeneous distribution of ERCC1 within tumors may be a source of discordance in the results obtained in various studies. Adding to the discordance may be the fact that there are four isoforms of ERCC1 and seemingly only one of these accounts for cisplatin sensitivity. It is possible that the antibodies used may be equally specific for the same isoforms, which contributes to the heterogeneity of results, in addition to the contribution from immunohistochemistry cutoff levels. Robust evidence in support of the use of ERCC1 to select treatment on an individual patient basis is lacking, and such results from ongoing trials are eagerly awaited in order to improve the possibilities for individualized chemotherapy with improved outcomes.