How to Cite
Abstract
Introduction. Long-term outcomes of metastatic urothelial cancer remain unsatisfactory: the 5-year survival rate for this disease is less than 15 %. It is important to develop and introduce into clinical practice new drugs, including targeted agents, and the individualization of systemic therapy for urothelial cancer based on molecular genetic analysis of tumor tissue. Erdafitinib, a new drug developed for the treatment of locally advanced and metastatic urothelial cancer with certain genetic alterations in the FGFR2 and FGFR3 receptors, was registered in Russia in 2023.
Materials and Methods. This work investigated the distribution of clinically relevant mutations/translocations affecting the FGFR2/3 genes in a large number urothelial cancer patients in Russia using a new test system developed on the basis of highly sensitive methods, such as digital droplet PCR and real-time PCR.
Results and Conclusion. 34 out of 182 patients (18.7 %) presented genetic aberrations. These aberrations included mutations R248C (n = 4), S249C (n = 16), G370C (n = 4) and Y373C (n = 8) in the FGFR3 gene, and translocation FGFR3-TACC3 (F17;T11) (n = 2). FGFR3 gene alterations were more frequent in upper urinary tract tumors: mutations/translocations were found in 5/8 (62.5 %) renal pelvic cancer patients, in 2/6 (33.3 %) ureteral cancer patients and in 21/120 (17.5 %) bladder cancer patients (p = 0,008). There was also an association with patient age and a tendency for more frequent detection of mutations in the localized form of the disease (stages 1-2).
Conclusion. The developed methods of mutation and translocation testing can be further used in clinical practice to determine the sensitivity of tumours to erdafitinib treatment.
References
Miyazaki J., Nishiyama H. Epidemiology of urothelial carcinoma. Int J Urol. 2017; 24(10): 730-734.-DOI: https://doi.org/10.1111/iju.13376.
Под ред. Каприна А.Д., Старинского В.В., Шахзадовой А.О. Злокачественные новообразования в России в 2021 году (заболеваемость и смертность). М.: МНИОИ им. П.А. Герцена − филиал ФГБУ «НМИЦ радиологии» Минздрава России. 2022; 252 с. URL: https://oncology-association.ru/wp-content/uploads/2022/11/zlokachestvennye-novoobrazovaniya-v-rossii-v-2021-g_zabolevaemost-i-smertnost.pdf.-ISBN: 978-5-85502-280-3. [Ed. by Kaprin A.D., Starinsky V.V., Shakhzadova A.O. Malignant neoplasms in Russia in 2021 (morbidity and mortality). Moscow: P.A. Herzen MNIOI - a branch of FGBU "NMRC Radiology" of the Ministry of Health of Russia. 2022; 252. URL: https://oncology-association.ru/wp-content/uploads/2022/11/zlokachestvennye-novoobrazovaniya-v-rossii-v-2021-g_zabolevaemost-i-smertnost.pdf.-ISBN: 978-5-85502-280-3. (In Rus)].
Гафанов Р.А., Дзидзария А.Г., Кравцов И.Б., Фастовец С.В. Системная терапия метастатического уротелиального рака: современные стандарты и рекомендации по лечению. РМЖ. Медицинское обозрение. 2018; 2(6): 28-35. URL: https://www.rusmedreview.com/upload/iblock/ff9/28-35.pdf. [Gafanov R.A., Dzidzaria A.G., Kravtsov I.B., Fastovets S.V. Systemic therapy of metastatic urothelial cancer: current standards and treatment guidelines. Russian Medical Inquiry = RMZh. Meditsinskoe Obozrenie. 2018; 6: 28-35. URL: https://www.rusmedreview.com/upload/iblock/ff9/28-35.pdf. (In Rus)].
Румянцев А.А. Лечение метастатического рака мочевого пузыря: исторические и современные аспекты. Медицинский совет. 2022; 16(22): 52-57.-DOI: https://doi.org/10.21518/2079-701X-2022-16-22-52-57. [Rumyantsev A.A. Treatment of metastatic bladder cancer: current and historical aspects. Meditsinskiy sovet = Medical Council. 2022; 22: 52-57.-DOI: https://doi.org/10.21518/2079-701X-2022-16-22-52-57. (In Rus)].
Клинические рекомендации. Рак мочевого пузыря. URL: https://oncology-association.ru/wp-content/uploads/2022/03/rak-mochevogo-puzyrya.pdf. [Clinical guidelines. Bladder cancer. URL: https://oncology-association.ru/wp-content/uploads/2022/03/rak-mochevogo-puzyrya.pdf. (In Rus)].
Roubal K., Myint Z.W., Kolesar J.M. Erdafitinib: A novel therapy for FGFR-mutated urothelial cancer. Am J Health Syst Pharm. 2020; 77(5): 346-351.-DOI: https://doi.org/10.1093/ajhp/zxz329.
Loriot Y., Necchi A., Park S.H., et al. Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2019; 381(4): 338-348.-DOI: https://doi.org/10.1056/NEJMoa1817323.
Hernández S., López-Knowles E., Lloreta J., et al. Prospective study of FGFR3 mutations as a prognostic factor in nonmuscle invasive urothelial bladder carcinomas. J Clin Oncol. 2006; 24(22): 3664-3671.-DOI: https://doi.org/10.1200/JCO.2005.05.1771.
Ross J.S., Wang K., Khaira D., et al. Comprehensive genomic profiling of 295 cases of clinically advanced urothelial carcinoma of the urinary bladder reveals a high frequency of clinically relevant genomic alterations. Cancer. 2016; 122(5): 702-711.-DOI: https://doi.org/10.1002/cncr.29826.
Necchi A., Madison R., Pal S.K., et al. Comprehensive Genomic Profiling of Upper-tract and Bladder Urothelial Carcinoma. Eur Urol Focus. 2021; 7(6): 1339-1346.-DOI: https://doi.org/10.1016/j.euf.2020.08.001.
Sfakianos J.P., Cha E.K., Iyer G., et al. Genomic Characterization of Upper Tract Urothelial Carcinoma. Eur Urol. 2015; 68(6): 970-977.-DOI: https://doi.org/10.1016/j.eururo.2015.07.039.
Chomczynski P., Sacchi N. The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloro-form extraction: twenty-something years on. Nat Protoc. 2006; 1(2): 581-585.-DOI: http://dx.doi.org/10.1038/nprot.2006.83.
R Core Team (2018). R Foundation for Statistical Computing, Vienna, Austria. URL: https://www.R-project.org.
Olmedillas-López S., García-Arranz M., García-Olmo D. Current and Emerging Applications of Droplet Digital PCR in Oncology. Mol Diagn Ther. 2017; 21(5): 493-510.-DOI: https://doi.org/10.1007/s40291-017-0278-8.
Helsten T., Elkin S., Arthur E., et al. The FGFR Landscape in Cancer: Analysis of 4,853 Tumors by Next-Generation Sequencing. Clin Cancer Res. 2016; 22(1): 259-267.-DOI: https://doi.org/10.1158/1078-0432.CCR-14-3212.
Necchi A., Madison R., Pal S.K., et al. Comprehensive Genomic Profiling of Upper-tract and Bladder Urothelial Carcinoma. Eur Urol Focus. 2021; 7(6): 1339-1346.-DOI: https://doi.org/10.1016/j.euf.2020.08.001.
Rizzo A., Mollica V., Santoni M., Massari F. Clinicopathological features of FGFR3 - mutated upper tract urothelial carcinoma: a genomic database analysis. Clin Genitourin Cancer. 2022; 20(5): 482-487.-DOI: https://doi.org/10.1016/j.clgc.2022.06.013.
Billerey C., Chopin D., Aubriot-Lorton M.H., et al. Frequent FGFR3 mutations in papillary non-invasive bladder (pTa) tumors. Am J Pathol. 2001; 158(6): 1955-1959.-DOI: https://doi.org/10.1016/S0002-9440(10)64665-2.
Aleksakhina S.N., Imyanitov E.N. Cancer therapy guided by mutation tests: current status and perspectives. Int J Mol Sci. 2021; 22(20): 10931.-DOI: https://doi.org/10.3390/ijms222010931.
Митюшкина Н.В., Имянитов Е.Н. Молекулярная диагностика нарушений в генах семейства FGFR. Вопросы онкологии. 2023; 69(3): 364-372.-DOI: https://doi.org/10.37469/0507-3758-2023-69-3-364-372. [Mitiushkina N.V., Imyanitov E.N. Molecular diag-nostics of aberrations in the FGFR family genes. Voprosy Onkologii = Problems in Oncology. 2023;69(3):364-372.-DOI: https://doi.org/10.37469/0507-3758-2023-69-3-364-372. (In Rus)].
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
© АННМО «Вопросы онкологии», Copyright (c) 2024