Терапия HER2-положительного рака желудка – обзор молекулярно-генетических особенностей сигнального пути, результатов клинических исследований.
pdf

Ключевые слова

HER2-положительный рак желудка
ERBB2 ген
трастузумаб

Аннотация

Рак желудка – это злокачественное заболевание с низкой общей выживаемостью, характеризующееся, в ряде случаев, агрессивным течением, несмотря на современные достижения хирургии, химиотерапии, молекулярно-генетических технологий. В связи с тем, что результаты лечения по-прежнему крайне неудовлетворительные, поиск новых терапевтических мишеней стал задачей номер один. В исторической перспективе HER2/neu-ориентированная таргетная терапия, продемонстрировавшая высокую эффективность в лечении рака молочной железы, послужила причиной для поиска высокого уровня экспрессии в других злокачественных новообразованиях. На протяжении десятилетий исследовались различные опухолевые локализации. Выяснено, что 10-20% аденокарцином желудка имеют высокую экспрессию HER2 рецептора. Результаты клинического исследования ToGA позволили включить трастузумаб в первую линию системной химиотерапии неоперабельного местнораспросраненного и метастатического HER2-положительного рака желудка. Настоящий обзор посвящен комплексному рассмотрению HER2-ориентированной таргетной терапии рака желудка, с раскрытием молекулярно-генетических особенностей сигнального пути, оценкой результатов существующих клинических исследований.

https://doi.org/10.37469/0507-3758-2023-69-1-45-54
pdf

Библиографические ссылки

Thrift AP, El-Serag HB. Burden of Gastric Cancer. Clin Gastroenterol Hepatol. 2020;18(3):534-542. doi:10.1016/j.cgh.2019.07.045.

Cisło M, Filip AA, Arnold Offerhaus GJ, et al. Distinct molecular subtypes of gastric cancer: from Laurén to molecular pathology. Oncotarget. 2018;9(27):19427-42. doi:10.18632/oncotarget.24827.

Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Prz Gastroenterol. 2019;14(1):26-38. doi:10.5114/pg.2018.80001.

Wang F-H, Shen L, Li J, et al. The Chinese Society of Clinical Oncology (CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer. Cancer Communications. 2019;39(1):10. doi:10.1186/s40880-019-0349-9.

Wagner AD, Syn NL, Moehler M, et al. Chemotherapy for advanced gastric cancer. Cochrane Database of Systematic Reviews. 2017; doi:10.1002/14651858.cd004064.pub4.

Alessandrini L, Manchi M, De Re V, et al. Proposed molecular and miRNA classification of gastric cancer. Int J Mol Sci. 2018;19(6):1683. doi:10.3390/ijms19061683.

Lei Z, Tan IB, Das K, et al. Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil. Gastroenterology. 2013;145(3):554-65. doi:10.1053/j.gastro.2013.05.010.

Sanjeevaiah A, Cheedella N, Hester C, et al. Gastric cancer: recent molecular classification advances, racial disparity, and management implications. J Oncol Pract. 2018;14(4):217-24. doi:10.1200/JOP.17.00025.

Chia N-Y, Tan P. Molecular classification of gastric cancer. Ann Oncol. 2016;27(5):763-9. doi:10.1093/annonc/mdw040.

Zhang W. TCGA divides gastric cancer into four molecular subtypes: implications for individualized therapeutics. Chin J Cancer. 2014;33(10):469-470. doi:10.5732/cjc.014.10117.

Smyth EC, Verheij M, Allum W, et al. Gastric cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27:v38-49. doi:10.1093/annonc/mdw350.

Moasser MM. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene. 2007;26(45):6469-87. doi:10.1038/sj.onc.1210477.

Schechter AL, Hung M-C, Vaidyanathan L, et al. The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science. 1985;229(4717):976-8. doi:10.1126/science.2992090.

Shih C, Padhy LC, Murray M, et al. Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature. 1981;290(5803):261-4. doi:10.1038/290261a0.

Bargmann CI, Hung M-C, Weinberg RA. The neu oncogene encodes an epidermal growth factor receptor-related protein. Nature. 1986;319(6050):226-30. doi:10.1038/319226a0.

Semba K, Kamata N, Toyoshima K, et al. A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. Proceedings of the National Academy of Sciences. 1985;82(19):6497-501; doi:10.1073/pnas.82.19.6497.

King CR, Kraus MH, Aaronson SA. Amplification of a novel v-erbB-related gene in a human mammary carcinoma. Science. 1985;229(4717):974-6. doi:10.1126/science.2992089.

Yamamoto T, Ikawa S, Akiyama T, et al. Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature. 1986;319(6050):230-4. doi:10.1038/319230a0.

Calderwood SK, Khaleque MA, Sawyer DB, et al. Heat shock proteins in cancer: chaperones of tumorigenesis. Trends Biochem Sci. 2006;31(3):164-72. doi:10.1016/j.tibs.2006.01.006.

Orlic-Milacic M, Neckers LM, Xu W. Signaling by ERBB2 [Internet]. Reatcome. 2021:20. Available from: https://reactome.org/content/detail/R-HSA-1227986.

Tao Y, Shen C, Luo S, et al. Role of Erbin in ErbB2-dependent breast tumor growth. Proc Natl Acad Sci USA. 2014;111(42). doi:10.1073/pnas.1407139111.

Gutierrez C, Schiff R. HER2: biology, detection, and clinical implications. Arch Pathol Lab Med. 2011;135(1):55-62. doi:10.5858/2010-0454-RAR.1.

Pohlmann PR, Mayer IA, Mernaugh R. Resistance to Trastuzumab in Breast Cancer. Clin Cancer Res. 2009;15(24):7479-7491. doi:10.1158/1078-0432.CCR-09-0636.

Mishra R, Hanker AB, Garrett JT. Genomic alterations of ERBB receptors in cancer: clinical implications. Oncotarget. 2017;8(69):114371-114392. doi:10.18632/oncotarget.22825.

Lee JW, Soung YH, Seo SH, et al. Somatic mutations of ERBB2 kinase domain in gastric, colorectal, and breast carcinomas. Clin Cancer Res. 2006;12(1):57-61. doi:10.1158/1078-0432.CCR-05-0976.

Natali PG, Nicotra MR, Bigotti A, et al. Expression of the p185 encoded by HER2 oncogene in normal and transformed human tissues. Int J Cancer. 1990;45(3):457-61. doi:10.1002/ijc.2910450314.

Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177-82. doi:10.1126/science.3798106.

Park JB, Rhim JS, Park SC, et al. Amplification, overexpression, and rearrangement of the erbB-2 protooncogene in primary human stomach carcinomas. Cancer Res. 1989;49(23):6605-9.

Jaehne J, Urmacher C, Thaler HT, et al. Expression of Her2/neu oncogene product p185 in correlation to clinicopathological and prognostic factors of gastric carcinoma. J Cancer Res Clin Oncol. 1992;118(6):474-9. doi:10.1007/BF01629433.

Drebin JA, Link VC, Greene MI. Monoclonal antibodies specific for the neu oncogene product directly mediate anti-tumor effects in vivo. Oncogene. 1988;2(4):387-94.

Drebin JA, Link VC, Stern DF, et al. Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies. Cell. 1985;41(3):697-706. doi:10.1016/s0092-8674(85)80050-7.

Akiyama T, Sudo C, Ogawara H, et al. The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science. 1986;232(4758):1644-6. doi:10.1126/science.3012781.

Stancovski I, Peles E, Levy RB, et al. Signal transduction by the neu/ebrB-2 receptor: A potential target for anti-tumor therapy. The Journal of Steroid Biochemistry and Molecular Biology. 1992;43(1-3):95-103. doi:10.1016/0960-0760(92)90192-L.

Lewis GD, Figari I, Fendly B, et al. Differential responses of human tumor cell lines to anti-p185HER2 monoclonal antibodies. Cancer Immunol Immunother. 1993;37(4):255-63. doi:10.1007/BF01518520.

Baselga J, Norton L, Albanell J, et al. Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res. 1998;58(13):2825-31.

Boekhout AH, Beijnen JH, Schellens JHM. Trastuzumab. The Oncologist [Internet]. 2011;16(6):800-10. doi:10.1634/theoncologist.2010-0035.

Trastuzumab Product Approval Information - Licensing Action 9/25/98. U.S. Drug&Food Administration. 1998. Available from: https://web.archive.org/web/20170128163102/https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm080591.htm.

Koeppen HKW, Wright BD, Burt AD, et al. Overexpression of HER2/neu in solid tumours: an immunohistochemical survey. Histopathology [Internet]. 2001;38(2):96-104. doi:10.1046/j.1365-2559.2001.01084.x.

Yano T, Doi T, Ohtsu A, et al. Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer. Oncology Reports. 2006. doi:10.3892/or.15.1.65.

Im SA, Lee KE, Nam E, et al. The prognostic significance of the overexpression of HER-2/ neu in Korean gastric carcinomas and the in vitro effects of Anti-HER-2/neu antibody on cell growth in the gastric carcinoma cell lines. Cancer Res Treat. 2003;35(2):109-16. doi:10.4143/crt.2003.35.2.109.

Gong SJ, Jin CJ, Rha SY, et al. Growth inhibitory effects of trastuzumab and chemotherapeutic drugs in gastric cancer cell lines. Cancer Lett. 2004;214(2):215-24. doi:10.1016/j.canlet.2004.04.029.

Matsui Y, Inomata M, Tojigamori M, Sonoda K, Shiraishi N, Kitano S. Suppression of tumor growth in human gastric cancer with HER2 overexpression by an anti-HER2 antibody in a murine model. Int J Oncol. 2005;27(3):681-5.

Rebischung C, Barnoud R, Stéfani L, et al. The effectiveness of trastuzumab (Herceptin) combined with chemotherapy for gastric carcinoma with overexpression of the c-erbB-2 protein. Gastric Cancer. 2005;8(4):249-52. doi:10.1007/s10120-005-0342-7.

Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet.. 2010;376(9742):687-97. doi:10.1016/S0140-6736(10)61121-X.

Nishikawa K, Takahashi T, Takaishi H, et al. Phase II study of the effectiveness and safety of trastuzumab and paclitaxel for taxane- and trastuzumab-naïve patients with HER2-positive, previously treated, advanced, or recurrent gastric cancer (JFMC45-1102). Int J Cancer. 2017;140(1):188-196. doi:10.1002/ijc.30383.

Wagner AD, Grabsch HI, Mauer M, et al. EORTC-1203-GITCG - the “INNOVATION”-trial: Effect of chemotherapy alone versus chemotherapy plus trastuzumab, versus chemotherapy plus trastuzumab plus pertuzumab, in the perioperative treatment of HER2 positive, gastric and gastroesophageal junction adenocarcinoma on pathologic response rate: a randomized phase II-intergroup trial of the EORTC-Gastrointestinal Tract Cancer Group, Korean Cancer Study Group and Dutch Upper GI-Cancer group. BMC Cancer. 2019;19(1). doi:10.1186/s12885-019-5675-4.

Fong C, Chau I. HER2 Inhibition in Gastric Cancer-Novel Therapeutic Approaches for an Established Target. Cancers (Basel). 2022;14(15):3824. doi:10.3390/cancers14153824.

Thuss-Patience PC, Shah MA, Ohtsu A, et al Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017;18(5):640-653. doi:10.1016/S1470-2045(17)30111-0.

Shitara K, Bang YJ, Iwasa S, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020;382(25):2419-2430. doi:10.1056/NEJMoa2004413.

Singh AP, Sharma S, Shah DK. Quantitative characterization of in vitro bystander effect of antibody-drug conjugates. J Pharmacokinet Pharmacodyn. 2016;43(6):567-582. doi:10.1007/s10928-016-9495-8.

Xu Y, Wang Y, Gong J, et al. Phase I study of the recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate RC48-ADC in patients with HER2-positive advanced solid tumors. Gastric Cancer. 2021;24(4):913-925. doi:10.1007/s10120-021-01168-7.

Chaganty BKR, Qiu S, Gest A, et al. Trastuzumab upregulates PD-L1 as a potential mechanism of trastuzumab resistance through engagement of immune effector cells and stimulation of IFNγ secretion. Cancer Lett. 2018;430:47-56. doi:10.1016/j.canlet.2018.05.009.

Stagg J, Loi S, Divisekera U, et al. Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy. Proc Natl Acad Sci U S A. 2011;108(17):7142-7. doi:10.1073/pnas.1016569108.

Janjigian YY, Maron SB, Chatila WK, et al. First-line pembrolizumab and trastuzumab in HER2-positive oesophageal, gastric, or gastro-oesophageal junction cancer: an open-label, single-arm, phase 2 trial. Lancet Oncol. 2020;21(6):821-831. doi:10.1016/S1470-2045(20)30169-8.

Grabsch H, Sivakumar S, Gray S, et al. HER2 expression in gastric cancer: Rare, heterogeneous and of no prognostic value - conclusions from 924 cases of two independent series. Cell Oncol. 2010;32(1-2):57-65. doi:10.3233/CLO-2009-0497.

Лицензия Creative Commons

Это произведение доступно по лицензии Creative Commons «Attribution-NonCommercial-NoDerivatives» («Атрибуция — Некоммерческое использование — Без производных произведений») 4.0 Всемирная.

Copyright (c) 2023 Анна Чайка, Мария Гусакова, Владимир Хомяков, Андрей Рябов