Dr Lee agreed that novel technology is crucial to developing reliable biomarkers for selecting targeted chemotherapy. “We should start designing trials using either comprehensive multiplex platforms that examine multiple cytotoxic resistance markers, or using newer technology such as whole-genome analysis, RNA sequencing, or proteomic analysis, which might provide a more accurate biomarker read-out compared to our IHC approach,” he said.

The development of biomarkers should be approached comprehensively, so as to include not only analysis of biomarkers on tumor cells, but also systematically analyze the tumor immune context and its microenvironment, said Dr Postel-Vinay. “Next generation sequencing techniques should also be exploited using complementary approaches assessing in parallel oncogene addiction, DNA repair status and immune landscape—searching for driver mutation, genomic scar, mutational load, and hot or cold characteristics of the tumor,” she said.

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But she also pointed out that many biomarkers can be analyzed only at specific cost and in specialized centers. “Medico-economic studies will therefore have to be performed to select the most relevant biomarker, or biomarker combination,” she said.

Dr Lee said that every new biomarker assessment technology should be explored for cytotoxic chemotherapy applications in NSCLC, including circulating biomarkers. “Liquid biopsy is fast emerging as a new diagnostic platform, which can capture the molecular diversity of the disease,” he said. “Serial testing can easily monitor spatial and temporal evolution of resistance cytotoxic biomarkers.”

In a recent editorial in Current Opinion in Oncology, the authors argued that because it is often difficult to obtain enough tumor sample from patients with NSCLC to perform genetic analysis to locate genetic biomarkers, liquid biopsy could prove particularly valuable.7 Analyzing serum or plasma of patients with NSCLC could quickly and easily provide measurements of the total tumor burden over time, and identify mutations that arise during treatment. But they also noted that extensive research is required before the method can be implemented in a clinical setting.

Dr Postel-Vinay and Dr Lee agreed that considerable challenges remain in the development of predictive biomarkers for targeted chemotherapy, and that further research is essential.


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