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Siglec 15 as a biomarker or a druggable molecule for non-small cell lung cancer

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Abstract

Lung cancer has been the main cause of cancer mortality worldwide. Furthermore, lung cancer rates of new cases per year evidenced a large incidence of this neoplasm in both men and women. Because there is no biomarker for early detection, it is frequently detected late, at an advanced state. The introduction of multiple lines of tyrosine kinase inhibitors in patients with EGFR, ALK, ROS1, and NTRK mutations has modified the therapy of lung cancer. Immunotherapy advances have resulted in substantial improvements in overall survival and disease-free survival, making immune checkpoint inhibitors (ICIs) a potential option for lung cancer treatment. Current PD-1/PD-L1/CTLA-4 immunotherapies have resulted in important response and survival rates. However, existing medicines only function in around 20% of unselected, advanced NSCLC patients, and primary and acquired resistance remain unsolved obstacles. Therefore, precise predictive indicators must be identified to choose the best patients for ICI treatment. Thus, Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) stands out as a potential tumor biomarker, with distinctive expression in normal tissues, in tumor immune involvement, and a high structural similarity to PD-L1. Understanding the tumor immune response and the search for new therapeutic targets leads to the improvement of therapeutic pathways directed at the tumor microenvironment. The present review aims to analyze Siglec-15 potential as a diagnostic, prognostic, and response biomarker in lung cancer, considering its results evidenced in the current literature.

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Fig. 1

Source: The author (2023). TAM tumor-associated macrophages

Fig. 2

Source: The author (2023). V-set variable domain, c2-set constant domain 2

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Data availability statement

The authors declare that the datasets generated during and/or analyzed during the current study are available in the manuscript.

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Acknowledgements

The authors would like to thank all the financial support by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco (FACEPE).

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This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Suely-Galdino Therapeutic Innovation Research Center (NUPIT-SG), Federal University of Pernambuco, Recife, Pernambuco, Brazil

    Rodrigo Santiago Moreira, Marillya Morais da Silva, Thiago Douberin da Silva, Maira Galdino da Rocha Pitta, Moacyr Jesus Barreto de Melo Rêgo & Michelly Cristiny Pereira

  2. Department of Surgery, Federal University of Pernambuco, Recife, Pernambuco, Brazil

    César Freire de Melo Vasconcelos & Gabriel Guerra Cordeiro

  3. Department of Clinic Medicine, Federal University of Pernambuco, Av. Prof. Moraes Rego, 1235, Recife, PE, Brazil

    Luiz Alberto Reis Mattos-Jr

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R. S.M and M.M da S wrote the main manuscript text C.F. de M.V; T. D. da S; and G.G.C prepared figures and table L. A.R.M.J; M.G.da R.P, and M.J.B.de M.R reviewed the manuscript M.C.P reviewed the manuscript and figures and table

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Correspondence to Michelly Cristiny Pereira.

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Moreira, R.S., da Silva, M.M., de Melo Vasconcelos, C.F. et al. Siglec 15 as a biomarker or a druggable molecule for non-small cell lung cancer. J Cancer Res Clin Oncol 149, 17651–17661 (2023). https://doi.org/10.1007/s00432-023-05437-z

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