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Cieľové molekuly novej generácie: ako môžu tieto molekuly zmeniť prístup k liečbe gastrointestinálnych nádorov


Authors: S. Naizabekova 1;  S. Dyikanbaeva 2;  F. Djumabaeva 2;  N. Dogdurbaeva 1;  V. Sloeva 1
Authors‘ workplace: Department of Chemotherapy, National Center for Oncology and Hematology, Bishkek, Kyrgyzstan 1;  Department of Oncology, I. K. Akhunbaev Kyrgyz State Medical Academy, Bishkek, Kyrgyzstan 2
Published in: Gastroent Hepatol 2026; 80(3): 239-249
Category: Gastrointestinal Oncology: Original Article
doi: https://doi.org/10.48095/ccgh2026239

Overview

Cieľom práce bolo určiť závislosť medzi molekulárnym profilom nádoru, klinickými parametrami priebehu ochorenia a dlhodobými výsledkami liečby. Štúdia bola realizovaná retrospektívnou analýzou údajov 75 pacientov s morfologicky potvrdenou diagnózou, s využitím komparatívnych, frekvenčných a stratifikovaných štatistických metód. Zistilo sa, že 84 % pacientov dosiahlo parciálnu regresiu, stabilizácia ochorenia bola zaznamenaná u 6 pacientov a frekvencia progresie dosiahla 8 %, čo umožnilo identifikovať vysokú primárnu účinnosť zvoleného lieku v prvej línii liečby. V skupine, ktorá pokračovala v monoterapii bez modifikácie protokolu, bola progresia ochorenia pozorovaná iba v 2,9 % prípadov, zatiaľ čo u pacientov, u ktorých bola liečba zmenená z dôvodu rezistencie, dosiahla frekvencia progresie 83,3 %. Najlepšie výsledky prežívania a kontroly ochorenia boli pozorované u pacientov s mutáciou v exóne 11 génu KIT, s mediánom prežívania bez progresie 30,2 mesiaca, frekvenciou parciálnej regresie nad 90 % a najnižšou úrovňou toxicity. V podskupine s mutáciou D842V génu PDGFRA prevládal progresívny priebeh, bola zaznamenaná nízka odpoveď na liečbu, skrátené obdobie klinickej stability a letálne výsledky vo viac ako 66 % prípadov pri prítomnosti metastáz. Výsledky stratifikovanej analýzy tiež potvrdili, že lokalizácia nádoru a štádium v čase diagnózy ovplyvňujú celkové prežívanie a prežívanie bez progresie. Aplikácia týchto výsledkov zdôvodňuje opodstatnenosť molekulárno-biologickej podpory v prvej línii liečby a umožňuje predikciu priebehu ochorenia. Získané údaje môžu byť využité onkológmi, molekulárnymi patomorfológmi a klinickými farmakológmi pri tvorbe individuálnych liečebných schém a pri rozhodovaní o modifikácii terapie na základe predikovanej citlivosti.

Klíčová slova:

gastrointestinální stromální tumory – inhibitory tyrosin kinázy – cílená léčba rakoviny – imatinib

...


Sources

1. Zhong L, Li Y, Xiong L et al. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Signal Transduct Target Ther 2021; 6 (1): 201. doi: 10.1038/s41392-021-00572-w.

2. Nakamura Y, Kawazoe A, Lordick F et al. Biomarker-targeted therapies for advanced-stage gastric and gastro-oesophageal junction cancers: an emerging paradigm. Nat Rev Clin Oncol 2021; 18 (8): 473–487. doi: 10.1038/s41571-021-00492-2.

3. Klug LR, Khosroyani HM, Kent JD et al. New treatment strategies for advanced-stage gastrointestinal stromal tumours. Nat Rev Clin Oncol 2022; 19 (5): 328–341. doi: 10.1038/s41571-022-00606-4.

4. Matsuoka T, Yashiro M. Molecular-targeted therapy toward precision medicine for gastrointestinal caner: current progress and challenges. World J Gastrointest Oncol 2021; 13 (5): 366–390. doi: 10.4251/wjgo.v13.i5.366.

5. Bai JW, Qiu SQ, Zhang GJ. Molecular and functional imaging in cancer-targeted therapy: current applications and future directions. Signal Transduct Target Ther 2023; 8 (1): 89. doi: 10.1038/s41392-023-01366-y.

6. Min HY, Lee HY. Molecular targeted therapy for anticancer treatment. Exp Mol Med 2022; 54 (10): 1670–1694. doi: 10.1038/s12276-022-00864-3.

7. El Fil S, Uwishema O, Ahmed AR et al. Immunotherapy in gastrointestinal cancers: current strategies and future directions-a literature review. Ann Med Surg 2025; 87 (1): 151–160. doi: 10.1097/MS9.0000000000002757.

8. Muto M, Sunakawa Y, Sandhir N et al. Real-world genomic landscape of gastrointestinal cancers in Asia and the Middle East using comprehensive circulating tumor DNA next-generation sequencing. Oncol Res Treat 2025; 48 (12): 1–17. doi: 10.1159/000545560.

9. Kaur R, Bhardwaj A, Gupta S. Cancer treatment therapies: traditional to modern approaches to combat cancers. Mol Biol Rep 2023; 50 (11): 9663–9676. doi: 10.1007/s11033-023-08809-3.

10. Brčić I, Argyropoulos A, Liegl-Atzwanger B. Update on molecular genetics of gastrointestinal stromal tumors. Diagnostics 2021; 11 (2): 194. doi: 10.3390/diagnostics11020194.

11. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53 (282): 457–481. doi: 10.2307/2281868.

12. NCI. Common Terminology Criteria for Adverse Events (CTCAE) v5.0. 2021 [online]. Available from: https: //ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.

13. ICH Harmonised Guideline. Integrated addendum to ICH E6 (R1): guideline for good clinical practice E6 (R2). 2016 [online]. Available from: https: //database.ich.org/sites/default/files/E6_R2_Addendum.pdf.

14. World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2013; 310 (20): 2191–2194. doi: 10.1001/jama.2013.281053.

15. Unk M, Jezeršek Novaković B, Novaković S. Molecular mechanisms of gastrointestinal stromal tumors and their impact on systemic therapy decision. Cancers 2023; 15 (5): 1498. doi: 10.3390/cancers15051498.

16. Cicala CM, Olivares-Rivas I, Aguirre-Carrillo JA et al. KIT/PDGFRA inhibitors for the treatment of gastrointestinal stromal tumors: getting to the gist of the problem. Expert Opin Investig Drugs 2024; 33 (3): 159–170. doi: 10.1080/13543784.2024.2318317.

17. Incorvaia L, De Biase D, Nannini M et al. KIT/PDGFRA variant allele frequency as prognostic factor in gastrointestinal stromal tumors (GISTs): results from a multi-institutional cohort study. Oncologist 2024; 29 (1): e141–e151. doi: 10.1093/oncolo/oyad206.

18. Schaefer IM, DeMatteo RP, Serrano C. The GIST of advances in treatment of advanced gastrointestinal stromal tumor. Am Soc Clin Oncol Educ Book 2022; 42 : 1–15. doi: 10.1200/EDBK_351231.

19. Blay JY, Kang YK, Nishida T et al. Gastrointestinal stromal tumours. Nat Rev Dis Primers 2021; 7 (1): 22. doi: 10.1038/s41572-021-00254-5.

20. Calderillo-Ruíz G, Pérez-Yepez EA, García-Gámez MA et al. Genomic profiling in GIST: implications in clinical outcome and future challenges. Neoplasia 2024; 48 : 100959. doi: 10.1016/j.neo.2023.100959.

21. Cannella R, Tabone E, Porrello G et al. Assessment of morphological CT imaging features for the prediction of risk stratification, mutations, and prognosis of gastrointestinal stromal tumors. Eur Radiol 2021; 31 (11): 8554–8564. doi: 10.1007/s00330-021-07961-3.

22. Moga DFC, Vlădoiu G, Frățilă AM et al. Understanding gastric GIST: from pathophysiology to personalized treatment. J Clin Med 2024; 13 (14): 3997. doi: 10.3390/jcm13143997.

23. Weeda YA, Kalisvaart GM, van Velden FH et al. Early prediction and monitoring of treatment response in gastrointestinal stromal tumors by means of imaging: a systematic review. Diagnostics 2022; 12 (11): 2722. doi: 10.3390/diagnostics12112722.

24. Ceausu M, Socea B, Ciobotaru VP et al. A multidisciplinary approach in the diagnostic challenge of GIST. Exp Ther Med 2021; 22 (4): 1063. doi: 10.3892/etm.2021.10497.

25. Palatresi D, Fedeli F, Danti G et al. Correlation of CT radiomic features for GISTs with pathological classification and molecular subtypes: preliminary and monocentric experience. Radiol Med 2022; 127 (2): 117–128. doi: 10.1007/s11547-021-01446-5.

26. Serrano C, Martín-Broto J, Asencio-Pascual JM et al. 2023 GEIS Guidelines for gastrointestinal stromal tumors. Ther Adv Med Oncol 2023; 15 : 17588359231192388. doi: 10.1177/175883592 31192388.

27. Judson I, Jones RL, Wong NA et al. Gastrointestinal stromal tumour (GIST): British Sarcoma Group clinical practice guidelines. Br J Cancer 2025; 132 (1): 1–10. doi: 10.1038/s41416-024-02672-0.

28. Li J, Huang Z, Zhou H et al. Survival outcomes and prognostic factors of advanced gastrointestinal stromal tumors: in the era of multiple tyrosine kinase inhibitors. J Gastrointest Oncol 2024; 15 (3): 931–945. doi: 10.21037/jgo-24-63.

29. Haller V, Reiff C, Hamacher R et al. Overall survival of patients with KIT-mutant metastatic GIST in the era of multiple kinase inhibitor availability. J Cancer Res Clin Oncol 2024; 150 (11): 489. doi: 10.1007/s00432-024-05965-2.

30. Rahimi-Ardabily A, Murdande S, Dong M et al. Liver resection for metastatic GIST tumor improves survival in the era of tyrosine kinase inhibitors: a systematic review and meta-analysis. Langenbecks Arch Surg 2023; 408 (1): 373. doi: 10.1007/s00423-023-03052-7.

31. von Mehren M, Heinrich MC, Shi H et al. Clinical efficacy comparison of avapritinib with other tyrosine kinase inhibitors in gastrointestinal stromal tumors with PDGFRA D842V mutation: a retrospective analysis of clinical trial and real-world data. BMC Cancer 2021; 21 (1): 291. doi: 10.1186/s12885-021-08013-1.

32. Liu L, Yu Z, Chen H et al. Imatinib adherence prediction using machine learning approach in patients with gastrointestinal stromal tumor. Cancer 2025; 131 (1): e35548. doi: 10.1002/cncr.35548.

33. Stefanou IK, Dovrolis N, Gazouli M et al. miRNAs expression pattern and machine learning models elucidate risk for gastric GIST. Cancer Biomark 2022; 33 (2): 237–247. doi: 10.3233/CBM-210173.

34. Beecroft JR, Brar S, Feng X et al. Pan-Canadian consensus recommendations for GIST management in high-and low-throughput centres across Canada. Ther Adv Med Oncol 2024; 16 : 17588359241266179. doi: 10.1177/17588359 241266179.

35. Renne SL, Cammelli M, Santori I et al. True mitotic count prediction in gastrointestinal stromal tumors: bayesian network model and PROMETheus (Preoperative Mitosis Estimator Tool) application development. J Med Internet Res 2024; 26: e50023. doi: 10.2196/50023.

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Paediatric gastroenterology Gastroenterology and hepatology Surgery

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