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.

References

  1. Lee SM, Falzon M, Blackhall F, et al. Randomized prospective biomarker trial of ERCC1 for comparing platinum and nonplatinum therapy in advanced non-small cell lung cancer: ERCC1 trial (ET). J Clin Oncol 2016 Nov 28. doi: 10.1200/JCO.2016.68.1841 [Epub ahead of print]
  2. Soria JC, Postel-Vinay S. ERCC1 as predictor of platinum benefit in non-small cell lung cancer. J Clin Oncol 2016 Nov 28. doi: 10.1200/JCO.2016.70.5053 [Epub ahead of print]
  3. Besse B, Olaussen KA, Soria JC. ERCC1 and RRM1: ready for prime time? J Clin Oncol 2013;31(8):1050-60. doi: 10.1200/JCO.2012.43.0900
  4. Buitrago DH, Patnaik SK, Kadota K, Kannisto E, Jones DR, Adusumilli PS. Small RNA sequencing for profiling microRNAs in long-term preserved formalin-fixed and paraffin-embedded non-small cell lung cancer tumor specimens. PLoS One. 2015;10(3):e0121521. doi: 10.1371/journal.pone.0121521
  5. Byron SA, Van Keuren-Jensen KR, Engelthaler DM, Carpten JD, Craig DW. Translating RNA sequencing into clinical diagnostics: opportunities and challenges. Nat Rev Genet. 2016;17(5):257-71. doi: 10.1038/nrg.2016.10
  6. Seeley EH, Cantrell PS, Walsh CM, et al. Mass spectrometry imaging determines biomarkers of early adaptive precision drug resistance in lung cancer. Abstract presented at: The 107th Annual Meeting of the American Association for Cancer Research; April 2016; New Orleans, LA.
  7. Buder A, Tomuta C, Filipits M. The potential of liquid biopsies. Curr Opin Oncol. 2016;28(2):130-4. doi: 10.1097/CCO.0000000000000267

Topics:

Lung Cancer Non-Small Cell Lung Cancer