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Integrative deep-sequencing analysis of cancer samples: discoveries and clinical challenges

The Pharmacogenomics Journal volume 13, pages 205–208 (2013)Cite this article

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Non-specific multimodal treatment of solid cancer including surgery, radiotherapy and systemic treatment with cytotoxic chemotherapy and targeted drugs in selected patients have improved oncological outcomes. However resistance, treatment failure and death rates still remain high particularly in advanced disease. Recently, high-throughput next-generation sequencing and arrays-based technologies have revolutionized biomedical research. However, the translation of deep-sequencing data into clinic in the emerging network biology seems to require additional understanding of dynamic complex signaling transduction pathway networks. Here, I discuss the results of the first published studies with deep-sequencing and transcriptomic analysis data of clinical samples from roughly 2400 breast cancer and 1125 medulloblastoma patients. The potential and challenges in how to adopt new genomic discoveries into novel robust biomarkers and cancer targets are also described.

Breast carcinoma is the leading cause of cancer-related mortality in women worldwide. The addition of targeted drugs, besides non-specific therapy, has substantially improved survival rates. Endocrine therapy with tamoxifen or aromatase inhibitors in premenopausal and postmenopausal estrogen receptor (ER)-positive patients, respectively, is standard treatment. Trastuzumab, an anti-HER2 antibody for (HER2) human epidermal growth factor type 2 receptor-positive women, added to chemotherapy improves overall survival in both adjuvant and metastatic setting.2 Previous work with microarrays-based differentially expressed genes has provided promising data. However, despite the wide use of gene expression profiling-based molecular subtypes (luminal A, luminal B, HER2-enriched and basal-like) and gene expression signatures (70-gene, 21-gene assays)1, 2 in research, their clinical utility remains controversial and awaits the results from underway phase 3-randomized trials. As cost drops, now breakthrough high-throughput genome-wide mapping technologies are being applied into clinical cancer genome-based potential for developing novel diagnostics and therapeutics.1 More recently six genomics studies in relatively large number of clinical samples in patients with various breast cancer subtypes have been reported in Nature.3, 4, 5, 6, 7, 8

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  1. Center for Biosystems & Genomic Network Medicine, Ioannina University, Ioannina, Greece

    D Roukos

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Correspondence to D Roukos.

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Roukos, D. Integrative deep-sequencing analysis of cancer samples: discoveries and clinical challenges. Pharmacogenomics J 13, 205–208 (2013). https://doi.org/10.1038/tpj.2012.51

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