Genetic and proteomic approaches to identify cancer drug targets

• Published in: British journal of cancer Vol. 106; no. 2; pp. 254 - 261
• Main Authors: Roti, G, Stegmaier, K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17-01-2012; Nature Publishing Group
• Subjects: Antineoplastic Agents - therapeutic use; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Chromatography; Drug Resistance; Epidemiology; Gene Expression; Genomics; Humans; Identification; Leukemia; Medical research; Medical sciences; mini-review; Minireview; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - metabolism; Oncology; Pediatrics; Pharmaceutical industry; Proteins; Proteomics; R&D; Research & development; Transcription factors; Tumors; United States > US; small-molecule library screening; chemical proteomics; cancer drug targets; drug discovery; protein target identification; chemical genomics; Human; Malignant tumor; Protein; Cancerology; Treatment; Targeted drug; protein target identifcation; Proteomics; Genetics; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2011.543

While target-based small-molecule discovery has taken centre-stage in the pharmaceutical industry, there are many cancer-promoting proteins not easily addressed with a traditional target-based screening approach. In order to address this problem, as well as to identify modulators of biological states in the absence of knowing the protein target of the state switch, alternative phenotypic screening approaches, such as gene expression-based and high-content imaging, have been developed. With this renewed interest in phenotypic screening, however, comes the challenge of identifying the binding protein target(s) of small-molecule hits. Emerging technologies have the potential to improve the process of target identification. In this review, we discuss the application of genomic (gene expression-based), genetic (short hairpin RNA and open reading frame screening), and proteomic approaches to protein target identification.