Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2024 Dec 11:14:1507658.
doi: 10.3389/fonc.2024.1507658. eCollection 2024.

Newly emerged ROS1 rearrangement in a patient with lung adenocarcinoma following resistance to immune checkpoint inhibitors: a case report

Jian Wang  1   2 , Bingyue Liu  3 , Qinhong Zheng  1 , Ruoshui Xiao  2 , Jianxin Chen  1
Affiliations
Case Reports

Newly emerged ROS1 rearrangement in a patient with lung adenocarcinoma following resistance to immune checkpoint inhibitors: a case report

Jian Wang et al. Front Oncol. .

Abstract

Background: ROS1, a member of the sevenless subfamily of tyrosine kinase insulin receptors, promotes tumor cell survival, proliferation, and metastasis by activating the JAK/STAT, PI3K/AKT, and MAPK/ERK pathways. It only accounts for about 2% of total NSCLC cases. No cases of acquired ROS-1 rearrangement have been reported worldwide.

Case presentation: We reported a case of lung adenocarcinoma without driver alteration that developed resistance to pembrolizumab and newly emerged CD74-ROS1 fusion, and achieved a partial response after entrectinib treatment.

Conclusions: We hypothesize that the newly emerged ROS1 rearrangement occurs as the subset of cells harboring ROS1 gradually becomes the predominant pathological type of adenocarcinoma following pembrolizumab treatment. We propose that new therapeutic targets may emerge for this patient population following long-term immunotherapy. Thus, we advocate for regular monitoring of tumor genetic status, which could yield unexpected benefits.

Keywords: ROS-1 rearrangement; case report; immune checkpoint inhibitors; lung adenocarcinoma; pembrolizumab; resistance.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Variations of occupation on mediastinum and both hilar areas by CT images during the treatment (red arrowheads). (A, B), February, 2022. (C, D), March, 2023. (E, F), April, 2024. (G, H), July, 2024.
Figure 2
Figure 2
Variations of occupation on brain areas by MRI images during the treatment (red arrowheads). (A, B), February, 2022. (C, D), February, 2023. (E, F), April, 2024. (G, H), July, 2024.
Figure 3
Figure 3
The variations of tumor marker CEA (normal range 0 to 5 ng/mL) and CA15-3 (normal range 0 to 25 U/mL) from March 13th to July 29th, 2024.
Figure 4
Figure 4
The overview of the approaches to diagnosis, and treatment regimens for each regimen. CBP, carboplatin; PEM, pemetrexed; Pembro, pembrolizumab; ENT, Entrectinib; PD, Progressive Disease; PR, partial response.
See this image and copyright information in PMC

References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clin. (2021) 71:209–49. doi: 10.3322/caac.21660 - DOI - PubMed
    1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA: Cancer J Clin. (2023) 73:17–48. doi: 10.3322/caac.21763 - DOI - PubMed
    1. Araghi M, Mannani R, Heidarnejad Maleki A, Hamidi A, Rostami S, Safa SH, et al. Recent advances in non-small cell lung cancer targeted therapy; an update review. Cancer Cell Int. (2023) 23:162. doi: 10.1186/s12935-023-02990-y - DOI - PMC - PubMed
    1. Nooreldeen R, Bach H. Current and future development in lung cancer diagnosis. Int J Mol Sci. (2021) 22. doi: 10.3390/ijms22168661 - DOI - PMC - PubMed
    1. Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S, et al. RET, ROS1 and ALK fusions in lung cancer. Nat Med. (2012) 18:378–81. doi: 10.1038/nm.2658 - DOI - PubMed

Publication types

LinkOut - more resources