Возможности персонализированного подхода в лечении распространенного рецидивирующего рака носоглотки

Рак носоглотки (назофарингеальная карцинома) – злокачественная опухоль, развивающаяся из неороговевающего эпителия носоглотки. В 2022 г. в мире зафиксировано более 530 тыс. новых случаев данной патологии. В РФ рак носоглотки составляет 0,3 % всех злокачественных новообразований и до 2 % всех злокачественных опухолей головы и шеи. пятилетняя общая выживаемость при заболевании I стадии составляет 90 %, Iv – 40 %. более чем у 40 % пациентов рак носоглотки диагностируют на Iv стадии.

В статье представлен клинический случай успешного лечения пациентки с распространенным рецидивирующим раком носоглотки.

1. Энциклопедия клинической онкологии: основные средства и методы диагностики и лечения злокачественных новообразований. Под ред. М.И. Давыдова. М: РЛС-2004, 2004. 1456 с.

2. Yang Y., Qu S., Li J. et al. Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncology 2021;22(8):1162–74. DOI: 10.1016/S1470-2045(21)00302-8

3. Al-Anazi A., Alanazi B., Alshanbari H.M. et al. Increased prevalence of EBV infection in nasopharyngeal carcinoma patients: a six-year cross-sectional study. Cancers (Basel) 2023;15(3):643. DOI: 10.3390/cancers15030643

4. Zhang J., Fang W., Qin T. et al. Co-expression of PD-1 and PD-L1 predicts poor outcome in nasopharyngeal carcinoma. Med Oncol 2015;32(3):86. DOI: 10.1155/2022/8537966

5. Blanchard P., Lee A., Marguet S. et al. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. Lancet Oncol 2015;16(6):645–55. DOI: 10.1016/S1470-2045(15)70126-9

6. Zhang Y., Li W.F., Liu X. et al. Nomogram to predict the benefit of additional induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: analysis of a multicenter, phase III randomized trial. Radiother Oncol 2018;129(1):18–22. DOI: 10.1016/j.radonc.2017.12.002

7. Ribassin-Majed L., Marguet S., Lee A.W. et al. What is the best treatment of locally advanced nasopharyngeal carcinoma? An individual patient data network meta-analysis. J Clin Oncol 2017;35(5):498–505. DOI: 10.1200/JCO.2016.67.4119

8. Chua D.T., Wei W.I., Sham J.S. et al. Treatment outcome for synchronous locoregional failures of nasopharyngeal carcinoma. Head Neck 2003;25(7):585–94. DOI: 10.1002/hed.10242

9. Toumi N., Ennouri S., Charfeddine I. et al. Local and lymph node relapse of nasopharyngeal carcinoma: a single-center experience. Ear Nose Throat J 2020;100(Suppl 5):795S–800S. DOI: 10.1177/0145561320908955

10. Poh S.S., Soong Y.L., Sommat K. et al. Retreatment in locally recurrent nasopharyngeal carcinoma: current status and perspectives. Cancer Commun (Lond) 2021;4(5):361–70. DOI: 10.1002/cac2.12159

11. Болотина Л В., Владимирова Л.Ю., Деньгина Н.В. и др. Опухоли головы и шеи. Злокачественные опухоли 2024;14(3s2): 160–82. DOI: 10.18027/2224-5057-2024-14-3s2-1.1-09

12. Shi S., Li B., Zhou P. et al. Analysis of the clinical efficacy and safety of anti-PD-1 immune checkpoint inhibitors in locally advanced nasopharyngeal cancer. Cancer Med 2024;13(14):e7359. DOI: 10.1002/cam4.7359

13. Zhou Z., Li P. et al. Mutational landscape of nasopharyngeal carcinoma based on targeted next-generation sequencing: implications for predicting clinical outcomes. Mol Med 2022;28(1):55. DOI: 10.1186/s10020-022-00479-4

14. Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012;487(7407):330–7. DOI: 10.1038/nature11252

15. Zehir A., Benayed R., Shah R.H. et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med 2017;23(6):703–13. DOI: 10.1038/nm.4333

16. Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015;517(7536):576–82. DOI: 10.1038/nature14129

17. Cheaib B., Auguste A., Leary A. The PI3K/Akt/mTOR pathway in ovarian cancer: therapeutic opportunities and challenges. Chin J Cancer 2015;34(1):4–16. DOI: 10.5732/cjc.014.10289

18. Vivanco I., Sawyers C.L. The phosphatidylinositol 3-kinase AKT pathway in human cancer. Nat Rev Cancer 2002;2(7):489–501. DOI: 10.1038/nrc839

19. Bessiere L., Todeschini A.-L. et al. A Hot-spot of In-frame ̀ duplications activates the oncoprotein AKT1 in juvenile granulosa cell tumors. eBioMedicine 2015;2(5):421–31. DOI: 10.1016/j.ebiom.2015.03.002

20. Auguste A., Bessiere L., Auguste A. et al. Molecular analyses ̀ of juvenile granulosa cell tumors bearing AKT1 mutations provide insights into tumor biology and therapeutic leads. Hum Mol Genet 2015;24(23):6687–98. DOI: 10.1093/hmg/ddv373

21. Chang M.T., Bhattarai T.S., Schram A.M. et al. Accelerating discovery of functional mutant alleles in cancer. Cancer Discov 2018;8(2):174–83. DOI: 10.1158/2159-8290.CD-17-0321

22. Yeh Y.-C., Ho H.-L., Wu Y.C. et al. AKT1 internal tandem duplications and point mutations are the genetic hallmarks of sclerosing pneumocytoma. Mod Pathol 2020;33(3):391–403. DOI: 10.1038/s41379-019-0357-y

23. Parikh C., Janakiraman V., Wu W.I. et al. Disruption of PH-kinase domain interactions leads to oncogenic activation of AKT in human cancers. Proc Natl Acad Sci USA 2012;109(47):19368–73. DOI: 10.1073/pnas.1204384109

24. Calleja V., Laguerre M., Parker P.J., Larijani B. et al. Role of a novel PH-kinase domain interface in PKB/Akt regulation: structural mechanism for allosteric inhibition. PLoS Biol 2009;7(1):e17. DOI: 10.1371/journal.pbio.1000017

25. Smyth L.M., Tamura K., Oliveira M. et al. Capivasertib, an AKT kinase inhibitor, as monotherapy or in combination with fulvestrant in patients with AKT1E17K-mutant, ER-positive metastatic breast cancer. Clin Cancer Res 2020;26(15):3947–57. DOI: 10.1158/1078-0432.CCR-19-3953

26. Kalinsky K., Zihan W., Kalinsky K. et al. Ipatasertib in patients with tumors with AKT mutations: results from the NCI-MATCH ECOG-ACRIn trial (EAY131) sub-protocol Z1K. Clin Cancer Res 2025. DOI: 10.1158/1078-0432.CCR-24-3431

27. Yu Z., Wei W., Liu H. et al. Efficient everolimus treatment for metastatic castration resistant prostate cancer with akt1 mutation: a case report. Onco Targets Ther 2021;14:5423–8. DOI: 10.2147/OTT.S334205

28. Giannakis M., Mu X.J., Shukla S.A. et al. Genomic correlates of immune-cell infiltrates in colorectal carcinoma. Cell Rep 2016;15(4):857–65. DOI: 10.1016/j.celrep.2016.03.075

29. Tredan O., Treilleux I., Wang Q. et al. Predicting everolimus ́ treatment efficacy in patients with advanced endometrial carcinoma: a GINECO group study. Target Oncol 2013;8(4):243–51. DOI: 10.1007/s11523-012-0242-9

30. Schneider T.C., de Wit D., Links T.P. et al. Everolimus in patients with advanced follicular-derived thyroid cancer: results of a phase II clinical trial. J Clin Endocrinol Metab 2017;102(2):698–707. DOI: 10.1210/jc.2016-2525

31. Bryce A.H., Egan J.B., Borad M.J. et al. Experience with precision genomics and tumor board, indicates frequent target identification, but barriers to delivery. Oncotarget 2017;8(16):27145–54. DOI: 10.18632/oncotarget.16057