ALK and ROS1 - Disease Drivers in Cancer
Anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) are related receptor tyrosine kinases (RTKs). Research studies have identified ALK and ROS as mutant C-terminal fusion proteins that are expressed in a wide range of cancers (1-10). Table 1 lists some of the ALK and ROS1 fusion partners that have been identified and the associated cancer types.
RTKs | Inhibitors | Fusion Partners | Associated Cancers |
|---|---|---|---|
ALK | Crizotinib5 | EML42,11, TFG1, KIF5B6, NPM7 | NSCLC1,2, ALCL7, CRC11 |
ROS1 | Crizotinib5 | FIG8, CD749, SLC34A29,11 | Glioblastoma8, Cholangiocarcinoma10, Ovarian cancer3, NSCLC1,4, CRC11 |
Table 1. Summary of ALK and ROS1 fusion partners and associated cancers. Abbreviations: ALCL=Anaplastic large cell lymphoma EML4=Echinoderm microtubule-associated protein-like 4 NPM=Nucleophosmin NSCLC=Non-small cell lung cancer TFG=TRK-fused gene
- Rikova, K. et al. (2007) Cell 131, 1190–1203.
- Takeuchi, K. et al. (2008) Clin Cancer Res 14, 6618–6624.
- Birch, A.H. et al. (2011) PLoS One 6, e28250.
- Rimkunas, V.M. et al. (2012) Clin Cancer Res 18, 4449–4457.
- D’Arcangelo, M. et al. (2013) Curr Opin Oncol 25, 121–129.
- Takeuchi, K. et al. (2009) Clin Cancer Res 15, 3143–3149.
- Morris, S.W. et al. (1994) Science 263, 1281–1284.
- Charest, A. et al. (2003) Genes Chromosomes Cancer 37, 58–71.
- Stumpfova, M. and Jänne, P.A. (2012) Clin Cancer Res 18, 4222–4224.
- Gu, T.L. et al. (2011) PLoS One 6, e15640.
- Aisner, D.L. et al (2013) Mol Cancer Res (Epub ahead of print)