Challenges for the development of immunotherapy in small-cell lung cancer
Main Article Content
Abstract
Small-cell lung cancer (SCLC) is a clinically aggressive cancer, and accounts for 15% of all types of lung cancer. SCLC is characterized by its rapid growth, early dissemination, and easy acquisition of multidrug resistance to chemotherapy. While most of the patients with SCLC are eligible to systemic chemotherapy owing to the presence of distant metastasis at the time of diagnosis, the median survival with the standard chemotherapy is less than 12 months. Numerous clinical trials, including molecular targeted therapy, have been conducted in hopes of developing a novel therapeutic strategy in SCLC, but eventuated disappointed results. Consequently, the standard chemotherapeutic regimen has not changed for three decades. Moreover, clinically beneficial therapeutic strategies for patients with relapsed-SCLC are extremely limited. Thus, effective treatment of SCLC has been leveling off in spite of the recent dramatic progress in the treatment of non-SCLC. Genomic analysis revealed that definitively targetable molecules with oncogenic driver activity were rarely detected
in SCLC. Therefore, immunotherapy rather than molecular targeted therapy is considered to be promising in the improvement of prognosis in patients with SCLC. Immune checkpoint inhibitors (ICIs) such as nivolumab and pembrolizumab have been approved for the treatment of the patients with non-SCLC, and have dramatically improved their prognosis. These ICIs exert antitumor effect via activating adaptive immunity. Some clinical trials have demonstrated promising effects of ICIs in the treatment of relapsed-SCLC. We have reported that trastuzumab, a humanized anti-human epidermal growth factor receptor 2 antibody, could exert remarkable antitumor effects against SCLC mainly through antibody-dependent cell-mediated cytotoxicity (ADCC) in preclinical models and clinical settings. ADCC is commonly recognized as one of the best ways to activate innate immunity. It is essential to clarify how to maximize the benefit of the immunotherapy in order to improve the prognosis of SCLC.
Keywords:
immunotherapy, small-cell lung cancer, immune checkpoint inhibitor, antibody dependent cell-mediated cytotoxicity
Article Details
How to Cite
MINAMI, Toshiyuki et al.
Challenges for the development of immunotherapy in small-cell lung cancer.
Medical Research Archives, [S.l.], v. 6, n. 6, june 2018.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/1817>. Date accessed: 08 may 2024.
doi: https://doi.org/10.18103/mra.v6i6.1817.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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21. Schultheis, A. M., Scheel, A. H., Ozretić, L., George, J., Thomas, R. K., Ha-gemann, T., et al. PD-L1 expression in small cell neuroendocrine carcinomas. Eur J Cancer 2015, 51 (3), 421-6. doi: 10.1016/j.ejca.2014.12.006.
22. Tsuruoka, K., Horinouchi, H., Goto, Y., Kanda, S., Fujiwara, Y., Nokihara, H., et al. PD-L1 expression in neuroendocrine tumors of the lung. Lung Cancer 2017, 108, 115-120. doi: 10.1016/j.lungcan.2017.03.006.
23. Shukuya, T., Carbone, D. P. Predic-tive Markers for the Efficacy of An-ti-PD-1/PD-L1 Antibodies in Lung Cancer. J Thorac Oncol 2016, 11 (7), 976-88. doi: 10.1016/j.jtho.2016.02.015.
24. Mutation Load Offers Biomarker in SCLC. Cancer Discov 2017, 7 (12), 1361. doi: 10.1158/2159-8290.CD-NB2017-154.
25. Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 2015, 372 (26), 2509-20. doi: 10.1056/NEJMoa1500596.
26. Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Ha-vel, J. J., et al. Cancer immunology. Muta-tional landscape determines sensitivity to PD-1 blockade in non-small cell lung can-cer. Science 2015, 348 (6230), 124-8. doi: 10.1126/science.aaa1348.
27. Pleasance, E. D., Stephens, P. J., O'Meara, S., McBride, D. J., Meynert, A., Jones, D., et al. A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature 2010, 463 (7278), 184-90. doi: 10.1038/nature08629.
28. Gazdar, A. F., Bunn, P. A., Minna, J. D. Small-cell lung cancer: what we know, what we need to know and the path forward. Nat Rev Cancer 2017, 17 (12), 765. doi: 10.1038/nrc.2017.106.
29. Reck, M., Luft, A., Szczesna, A., Havel, L., Kim, S. W., Akerley, W., et al. Phase III Randomized Trial of Ipilimumab Plus Etoposide and Platinum Versus Place-bo Plus Etoposide and Platinum in Exten-sive-Stage Small-Cell Lung Cancer. J Clin Oncol 2016, 34 (31), 3740-3748. doi: 10.1200/JCO.2016.67.6601.
30. Garrido, F., Aptsiauri, N., Doorduijn, E. M., Garcia Lora, A. M., van Hall, T. The urgent need to recover MHC class I in can-cers for effective immunotherapy. Curr Opin Immunol 2016, 39, 44-51. doi: 10.1016/j.coi.2015.12.007.
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