ROS1 is a therapeutic target in NSCLC, with gene fusions occurring in 1–2%
of patients.1,2
Patients with ROS1+ NSCLC require an effective treatment with both systemic and central nervous system (CNS) activity.3–6
up to
40%
of patients with advanced ROS1+ NSCLC have CNS metastases at
diagnosis3,4
up to
47%
of ROS1+ patients have CNS as their first and only site of progression3,7

The most common sites of metastasis for patients with all types of stage IV lung cancer8

CNS 12.4%8
(36% for ROS1+ NSCLC)3Lung 18.5%8
Bone 16.4%8
Despite advances in therapy for ROS1+ NSCLC, additional treatment options are needed to improve clinical outcomes3
High-quality molecular testing, such as FISH and NGS, is needed to confirm patients with actionable ROS1 gene fusions9

- NGS is emerging as a technology with the sensitivity and accuracy necessary to identify all ROS1 gene fusions with a single test9,13–19
The ROS1 protein plays an important role in healthy tissue and if altered by fusion events or mutations drives cancer through aberrant signalling20-22
ROS1 gene fusions create oncogenic proteins22
- The ROS1 gene can combine with multiple other gene partners to create an oncogenic fusion protein22
- So far ~55 gene fusions have been detected28

The oncogenic ROS1 protein drives cancer through aberrant signalling22
- The oncogenic fusion or mutated ROS1 protein constitutively activates signalling cascades implicated in cell proliferation, survival and angiogenesis22


Footnotes:
CNS, central nervous system; FISH, fluorescence in situ hybridisation; IHC, immunohistochemistry; NGS, next-generation sequencing; NSCLC, non-small cell lung cancer; RT-PCR, reverse transcription polymerase chain reaction.
- 1
Bergethon K, et al. J Clin Oncol 2012;30:863–870.
- 2
Dugay F, et al. Oncotarget 2017;8:53336–53351.
- 3
Patil T, et al. J Thorac Oncol 2018;13:1717–1726.
- 4
Gainor JF, et al. JCO Precis Oncol 2017. DOI: 10.1200/PO.17.00063.
- 5
Mazières J, et al. J Clin Oncol 2015;33:992–999.
- 6
Wu YL, et al. J Clin Oncol 2018;36:1405–1411.
- 7
Xu H, et al. Cancer Med 2020;9:3328–3336.
- 8
Oikawa A, et al. Oncol Lett 2012;3:629–634.
- 9
Bubendorf L, et al. Virchows Arch 2016;469:489–503.
- 10
Planchard D. Ann Oncol 2018;29:iv192–iv237.
- 11
International Association for the Study of Lung Cancer. IASLC Atlas of ALK and ROS1 testing in lung cancer. Available at: https://www.iaslc.org/research-education/publications-resources-guidelines/iaslc-atlas-alk-and-ros1-testing-lung-cancer (Accessed November 2020).
- 12
Rossi G, et al. Lung Cancer (Auckl) 2017:8:45–55.
- 13
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Non-Small Cell Lung Cancer. V.6.2020, 2020. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf (Accessed November 2020).
- 14
Diaz L, Bardelli A. J Clin Oncol 2014;32:579–586.
- 15
Shan L, et al. PLoS One 2015;10:e0120422.
- 16
Cao B, et al. Onco Targets Ther 2016;31:131–138.
- 17
Zheng Z, et al. Nat Med 2014;20:1479–1484.
- 18
Drilon A, et al. Clin Cancer Res 2015;21:3631–3639.
- 19
Grada A, Weinbrecht K. J Invest Dermatol 2013;133:e11.
- 20
Birchmeier C, et al. Proc Natl Acad Sci U S A 1987;84: 9270–9274.
- 21
Rikova K, et al. Cell 2007;131:1190–1203.
- 22
Gainor J, Shaw A. Oncologist 2013;18:865–875.
- 28
Drillon et al. Clinical Oncology 2021; 18:35-55
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