Biomarkers of resistance to cetuximab in head and neck squamous cell carcinoma (HNSCC)

Surikova, E.I.; Kit, O.I.; Neskubina, I.V.; Frantsiyants, E.M.; Vladimirova, L.Y.; Lyanova, A.A.; Engibaryan, M.A.; Shalashnaya, E.V.; Aedinova, I.V.; Ulianova, Y.V.; Volkova, V.L.; Pustovaya, I.V.; Ezhova, M.

Авторы: Surikova Ekaterina I., Kit Oleg I., Neskubina Irina V., Frantsiyants Elena M., Vladimirova Liubov Yu, Lyanova Aza A., Engibaryan Marina A., Shalashnaya Elena V., Aedinova Irina V., Ulianova Yulia V., Volkova Viktoriya L., Pustovaya Irina Viktorovna, Ezhova Maria
Журнал: Journal of Clinical Oncology
Том: 37
Номер: 15_suppl
Год издания: 2019
Издательство: American Society of Clinical Oncology
Местоположение издательства: United States
Первая страница: e17523
Последняя страница: e17523
DOI: 10.1200/jco.2019.37.15_suppl.e17523
Аннотация: Background: Treatment of advanced HNSCC (T3 and T4) involves the use of anti-EGFR monoclonal antibodies targeting the EGF-EGFR and VEGF-VEGFR cascades responsible for the cell proliferation, differentiation, invasion, metastasis, angiogenesis and apoptosis. The purpose of the study was the search for biomarkers of resistance to cetuximab in HNSCC patients. Methods: Tumor biopsy was performed in patients with HNSCC (n = 40) (Т3-4N0-1M0) before and after two cycles of chemotherapy with cetuximab - 400 mg/m2 administered on day 1 and 250 mg/m2 per week, cisplatin 100 mg/m2 on day 1, fluorouracil 1000 mg/m2 - 96-hour continuous infusion. Patients were divided into group 1 (progression, n = 11) and group 2 (stabilization and partial remission, n = 29). Levels of VEGF-A (pg/mL) (BenderMedSystem, Austria) and TGF-β (pg/mL) (eBioscience, USA) were determined in biopsy samples by ELISA, and the VEGF-A/TGF-β ratio was calculated. Statistical analysis of the results was performed using the Statistica 10.0 program with M±m determination. Differences were considered significant at p < 0.05. Results: Before treatment, levels of VEGF-A in biopsy samples were 634.8±37.2, TGF-β – 1092.5±71.9, and VEGF-A/TGF-β – 0.58±0.03. After 2 cycles of chemotherapy with cetuximab, results in group 1 for VEGF-A were 680.3±41.2, TGF-β – 1773.7±111.4, and VEGF-A/TGF-β – 0.384±0.021; in group 2: VEGF-A – 487.7±26.1, TGF-β – 572.3±34.7, and VEGF-A/TGF-β – 0.85±0.043. Thus, after 2 cycles of chemotherapy with cetuximab, TGF-β in group 1 increased by 1.6 times and VEGF-A/TGF-β – by 1.5 times (p < 0.05). In group 2, VEGF-A decreased by 1.3 times, TGF-β by 1.9 times, and VEGF-A/TGF-β increased by 1.46 times (p < 0.05). Conclusions: Decreased levels of markers and increased VEGF-A/TGF-β can predict cetuximab efficacy. Increased TGF-β and reduced VEGF-A/TGF-β allow predicting resistance to chemotherapy with cetuximab.
Добавил в систему: Владимирова Любовь Юрьевна

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Biomarkers of resistance to cetuximab in head and neck squamous cell carcinoma (HNSCC)статья

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