PREVALENCE OF ALK-ABERRATIONS IN PATIENTSWITH NON-SMALL CELL LUNG CANCER IN THE REPUBLIC OF BASHKORTOSTAN

Lung cancer occupies the top rank among all cancers. Non-small cell lung cancer is its most frequent histotype. One of the main therapeutic targets in this disease is ALK translocations.
The aim of the study. To describe the algorithms of examination of patients with this nosology in the Republic of Bashkortostan and to analyze the prevalence of ALK-translocation in patients with non-small cell lung cancer with assessment of therapy efficacy.
Material and methods. The material of the study was tumor of patients coming for research from the Republican Clinical Oncologic Dispensary. Immunohistochemistry and FISH were the methods of the study. Data on patients' response to therapy were taken from patients' medical records.
Results. The results of the study showed that 5.1% of patients were ALK positive, demonstrating an average prevalence of ALK gene rearrangement in our population compared to literature data. However, therapy does not have a long-term response for all patients.
Conclusion. For patients who do not show a satisfactory therapeutic response, the use of molecular genetic testing to search for resistance mutations may be promising, which will allow a more correct selection of the next line of treatment.

1. Mufazalov F. F., Mansurov K. V. Role of positron emission tomography in diagnostics and assessment of the distribution of non-small cell lung cancer. Bashkortostan Medical Journal. 2019;5:83. (In Russ)

2. Slugin E.N., Levchenko E.V., Imyanitov E.N., [et al]. Evaluation of the role of egfr mutation in determining the tactic of surgical treatment of non-small cell lung cancer. Voprosy Onkologii. 2021;3:315-322. (In Russ) DOI: 10.37469/0507-3758-2021-67-3-315-322.

3. Meyer M.L., Peters S., Mok T.S., [et al]. Lung Cancer Research and Treatment: Global Perspectives and Strategic Calls to Action. Ann Oncol. 2024;14:S0923-7534(24)04055-9. URL:.https://pubmed.ncbi.nlm.nih.gov/39413875/ (date of aссess: 06.11.2024). (In Engl).

4. Laktionov K.K., Sarantseva K.A., Breder V.V., [et al]. Place of immuno-oncology in the treatment of non-small cell lung cancer // Malignant Tumors. 2016;3:17-22. (In Russ). DOI: 10.18027/2224-5057-2016-3-17-24

5. Roskoski R.Jr. Targeted and cytotoxic inhibitors used in the treatment of lung cancers. Pharmacol Res. 2024;209:107465. (In Engl). DOI: 10.1016/j.phrs.2024.107465.

6. Yu L., Yang R., Long Z., [et al]. Targeted therapy of non-small cell lung cancer: mechanisms and clinical trials. Front Oncol. 2024;14:1451230. (In Engl). DOI: 10.3389/fonc.2024.1451230.

7. Kharagezov D.A., Lazutin Yu.N., Mirzoyan E.A., [et al]. A clinical case of pulmonary mucormycosis in a child with acute lymphoblastic leukemia. South Russian Journal of Cancer. 2021;2(4):38-47. (In Russ) DOI:10.37748/2686-9039-2021-2-4-5

8. Xia L., Liu Y., Wang Y. PD-1/PD-L1 Blockade Therapy in Advanced Non-Small-Cell Lung Cancer: Current Status and Future Directions. Oncologist. 2019;24:S31-S41. (In Engl). DOI: 10.1634/theoncologist.2019-IO-S1-s05.

9. Dantoing E., Piton N., Salaün M., [et al]. Anti-PD1/PD-L1 Immunotherapy for Non-Small Cell Lung Cancer with Actionable Oncogenic Driver Mutations. Int J Mol Sci. 2021;22(12):6288. (In Engl). DOI: 10.3390/ijms22126288

10. Jawed R., Bhatti H., Khan A. Genetic profile of ferroptosis in non-small cell lung carcinoma and pharmaceutical options for ferroptosis induction. Clin Transl Oncol. 2024;1-20. (In Engl). DOI: 10.1007/s12094-024-03754-4.

11. Elshatlawy M., Sampson J., Clarke K., [et al]. EML4-ALK biology and drug resistance in non-small cell lung cancer: a new phase of discoveries. Mol Oncol. 2023;17(6):950-963. (In Engl). DOI: 10.1002/1878-0261.13446.

12. Sakaeva D.D., Bulavina I.S. Target therapy of metastatic head mobile injury in patients with alk-positive non-small cell lung cancer. Modern Oncology. 2021;(4):685-694. (In Russ) DOI: 10.26442/18151434.2021.4.201344.

13. Sainoga T.V. Screening of ALK gene mutation in NSCLC by immunohistochemical method: regional experience. Voprosy Onkologii. 2023;3:132-133. (In Russ).

14. Demidova I.A., Tsepenshchikova E.O., Barinov A.A., [et al]. Determination of rearrangements in ALK gene in selected russian population of patients with non-small cell lung cancer. Malignant tumours. 2013;(3):3-9. (In Russ.) DOI: 10.18027/2224-5057-2013-3-3-9.

15. Kolesnik, A. P., Shevchenko, A. I., Kadzhoyan, A.V. [et al]. ALK inhibitors in the treatment of ALK-positive non-small cell lung cancer (literature review). Klinicheskaya onkologiya. 2018;4:254–257. (In Russ)

16. Gorzelak-Magiera A., Domagała-Haduch M., Kabut J., [et al]. The Use of Anaplastic Lymphoma Kinase Inhibitors in Non-Small-Cell Lung Cancer Treatment-Literature Review. Biomedicines. 2024 Oct 11;12(10):2308. (In Engl). DOI: 10.3390/biomedicines12102308.

17. Laktionov K. K., Reutova E. V., Sarantseva K. A. ALK-positive non-small cell lung cancer and methods of its treatment: a review of the literature. Farmateka. 2015;18: 76. (In Russ)

18. Borbat A. M., Yatsenko I. V. Protocol for evaluation of histologic micropreparation for molecular genetic studies. Molecular Medicine. 2021;19(2):3-7. (In Russ) DOI: 10.29296/24999490-2021-02-01

19. Laktionov K. K., Kruteleva S. Yu. V. Modern approaches to therapy of ALK-positive non-small cell lung cancer. Medical Council. 2021;4:16-22. (In Russ) DOI: 10.21518/2079-701X-2021-4S-16-22

20. Tímár J., Lotz G., Rásó E., [et al]. Az ALK-pozitív tüdõrák korszerû diagnosztikája [Molecular diagnostics of ALK-positive lung cancer]. Magy Onkol. 2017;61(3):301-311. (In Hungarian)

21. Asao T., Takahashi F., Takahashi K. Resistance to molecularly targeted therapy in non-small-cell lung cancer. Respir Investig. 2019;57(1):20-26. (In Engl) DOI: 10.1016/j.resinv.2018.09.001.