"Omics"-Informed Drug and Biomarker Discovery: Opportunities, Challenges and Future Perspectives

Abstract

The pharmaceutical industry faces unsustainable program failure despite significant increases in investment. Dwindling discovery pipelines, rapidly expanding R&D budgets and increasing regulatory control, predict significant gaps in the future drug markets. The cumulative duration of discovery from concept to commercialisation is unacceptably lengthy, and adds to the deepening crisis. Existing animal models predicting clinical translations are simplistic, highly reductionist and, therefore, not fit for purpose. The catastrophic consequences of ever-increasing attrition rates are most likely to be felt in the developing world, where resistance acquisition by killer diseases like malaria, tuberculosis and HIV have paced far ahead of new drug discovery. The coming of age of Omics-based applications makes available a formidable technological resource to further expand our knowledge of the complexities of human disease. The standardisation, analysis and comprehensive collation of the "data-heavy" outputs of these sciences are indeed challenging. A renewed focus on increasing reproducibility by understanding inherent biological, methodological, technical and analytical variables is crucial if reliable and useful inferences with potential for translation are to be achieved. The individual Omics sciences-genomics, transcriptomics, proteomics and metabolomics-have the singular advantage of being complimentary for cross validation, and together could potentially enable a much-needed systems biology perspective of the perturbations underlying disease processes. If current adverse trends are to be reversed, it is imperative that a shift in the R&D focus from speed to quality is achieved. In this review, we discuss the potential implications of recent Omics-based advances for the drug development process.

Keywords: drug discovery; genomics; metabolomics; omics; proteomics.

Figure 1

Drug discovery and development timeline. The current drug approval pipeline can take ~15 years. It is estimated that from 5,000–10,000 compounds only one new drug reaches the market. (Adapted from http://cmidd.northwestern.edu/files/2015/10/Drug_RD_Brochure-12e7vs6.pdf [10]; http://www.phrma.org/sites/default/files/pdf/rd_brochure_022307.pdf [11])