Despite the development of molecular classifications, and prognostic and predictive gene-expression signatures, microarray-based studies have not yielded definitive answers to many of the questions that remain germane for the successful implementation of personalized medicine. Similar challenges are likely to be encountered in translating next-generation sequencing data into clinically useful information.
- The development of novel high-throughput functional assays that could interrogate the consequences of nucleic acid variations in a large number of loci and in many different genes at the same time are urgently needed in the laboratory.
- The functional significance of mutations affecting non-protein-coding genes will require the development of imaginative new functional assays.
- Training of translational and clinical researchers to understand the intricate complexity of interpreting massively parallel sequencing results and its derivatives, in conjunction with their functional consequences.
- The current methods to determine the biological significance of novel nucleic acid variations are tedious and low throughput in the laboratory.
- The bioinformatics tools to distinguish passenger from driver mutations are still nascent.
- These tools’ sensitivity, and specificity can vary according to context, stage of tumor development, and clinical scenario.
- The functional consequences of somatic mutations in tumors may also be amplified or diminished by the genomic background of the host.
- New prognostic signatures or markers could be useful, but those currently on the horizon are unlikely to be sufficiently accurate to safely justify withholding adjuvant chemotherapy.
- No single investigator can fully comprehend and control each of the multitude of analytical steps.
- Translational medicine is a multidisciplinary endeavor; contribution from individual’s with expertise in various fields will be required.
Weigelt B, Pusztai L, Ashworth A, Reis-Filho JS. Challenges translating breast cancer gene signatures into the clinic. Nat Rev Clin Oncol [Epub ahead of print]. [abstract]