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

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

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  •  CNS 12.4%8 
     (36% for ROS1+    NSCLC)3

  •  Lung 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

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Testing for ROS1 rearrangement should be systematically carried out in advanced NSCLC10

  • ROS1 testing involves the detection of ROS1 gene rearrangements or overexpression of ROS1-fusion proteins11
  • FISH, IHC and RT-PCR are currently used in routine clinical practice:
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NGS is increasingly being used and is a sensitive and accurate test to identify most ROS1 gene fusions with a single test9,13–19

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FISH has been the standard approach to detecting ROS1 gene rearrangements10

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IHC may be used to identify candidate tumours but due to low specificity, other testing is required to confirm the diagnosis10*

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RT-PCR has good sensitivity and specificity; however, its use may be limited by the presence of numerous ROS1 fusion partners, both identified and still unknown, and difficulties in obtaining good-quality RNA12

  • 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
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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
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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