Research Progress on Molecular Characteristics and Targeted Therapy of Uterine Serous Carcinoma

doi:10.12280/gjfckx.20210973

Abstract

Abstract:

As a special type of endometrial carcinoma, uterine serous carcinoma (USC) has high malignant degree, high risk of invasion and metastasis and poor prognosis. With the deepening of molecular research on endometrial carcinoma, molecular characteristics have been applied to the pathological diagnosis, treatment and prognosis of endometrial carcinoma. A variety of gene mutations have been found in USC, which may help to guide clinical diagnosis and therapy. And the specific molecular changes provide potential therapeutic targets for USC targeted therapy. At present, a variety of targeted therapies, including HER2 inhibitors, immune checkpoint inhibitors, anti-angiogenesis therapy, PI3K pathway inhibitors, PARP inhibitors and so on, have been used in the clinical treatment of the disease. Targeted therapy is expected to become a new breakthrough in the treatment of USC.

Key words: Endometrial neoplasms, Molecular targeted therapy, Genes,erbB-2, Angiogenesis inhibitors, Phosphatidylinositol 3-kinase

XIE Yun-kai, KONG Wei-min. Research Progress on Molecular Characteristics and Targeted Therapy of Uterine Serous Carcinoma[J]. Journal of International Obstetrics and Gynecology, 2022, 49(3): 278-281.

References 30

[1]	Zheng W, Xiang L, Fadare O, et al. A proposed model for endometrial serous carcinogenesis[J]. Am J Surg Pathol, 2011, 35(1):e1-e14. doi: 10.1097/PAS.0b013e318202772e. doi: 10.1097/PAS.0b013e318202772e
[2]	Black C, Feng A, Bittinger S, et al. Uterine Papillary Serous Carcinoma: A Single-Institution Review of 62 Cases[J]. Int J Gynecol Cancer, 2016, 26(1):133-140. doi: 10.1097/IGC.0000000000000569. doi: 10.1097/IGC.0000000000000569
[3]	del Carmen MG, Birrer M, Schorge JO. Uterine papillary serous cancer: a review of the literature[J]. Gynecol Oncol, 2012, 127(3):651-661. doi: 10.1016/j.ygyno.2012.09.012. doi: 10.1016/j.ygyno.2012.09.012
[4]	Lee EK, Fader AN, Santin AD, et al. Uterine serous carcinoma: Molecular features, clinical management, and new and future therapies[J]. Gynecol Oncol, 2021, 160(1):322-332. doi: 10.1016/j.ygyno.2020.10.017. doi: 10.1016/j.ygyno.2020.10.017
[5]	Cree IA, White VA, Indave BI, et al. Revising the WHO classification: female genital tract tumours[J]. Histopathology, 2020, 76(1):151-156. doi: 10.1111/his.13977. doi: 10.1111/his.13977 pmid: 31846528
[6]	Koh WJ, Abu-Rustum NR, Bean S, et al. Uterine Neoplasms, Version 1. 2018, NCCN Clinical Practice Guidelines in Oncology[J]. J Natl Compr Canc Netw,2018, 16(2):170-199. doi: 10.6004/jnccn.2018.0006. doi: 10.6004/jnccn.2018.0006
[7]	Remmerie M, Janssens V. Targeted Therapies in Type II Endometrial Cancers: Too Little, but Not Too Late[J]. Int J Mol Sci, 2018, 19(8):2380. doi: 10.3390/ijms19082380. doi: 10.3390/ijms19082380
[8]	Schultheis AM, Martelotto LG, De Filippo MR, et al. TP53 Mutational Spectrum in Endometrioid and Serous Endometrial Cancers[J]. Int J Gynecol Pathol, 2016, 35(4):289-300. doi: 10.1097/PGP.0000000000000243. doi: 10.1097/PGP.0000000000000243 pmid: 26556035
[9]	Erickson BK, Najjar O, Damast S, et al. Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study[J]. Gynecol Oncol, 2020, 159(1):17-22. doi: 10.1016/j.ygyno.2020.07.016. doi: 10.1016/j.ygyno.2020.07.016 pmid: 32709539
[10]	Fruman DA, Chiu H, Hopkins BD, et al. The PI3K Pathway in Human Disease[J]. Cell, 2017, 170(4):605-635. doi: 10.1016/j.cell.2017.07.029. doi: S0092-8674(17)30865-6 pmid: 28802037
[11]	Le Gallo M, O′Hara AJ, Rudd ML, et al. Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes[J]. Nat Genet, 2012, 44(12):1310-1315. doi: 10.1038/ng.2455. doi: 10.1038/ng.2455
[12]	Yumimoto K, Nakayama KI. Recent insight into the role of FBXW7 as a tumor suppressor[J]. Semin Cancer Biol, 2020, 67(Pt 2):1-15. doi: 10.1016/j.semcancer.2020.02.017. doi: 10.1016/j.semcancer.2020.02.017 pmid: 32113998
[13]	Kandoth C, Schultz N, Cherniack AD, et al. Integrated genomic characterization of endometrial carcinoma[J]. Nature, 2013, 497(7447):67-73. doi: 10.1038/nature12113. doi: 10.1038/nature12113
[14]	Fader AN, Roque DM, Siegel E, et al. Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu[J]. J Clin Oncol, 2018, 36(20):2044-2051. doi: 10.1200/JCO.2017.76.5966. doi: 10.1200/JCO.2017.76.5966
[15]	Fader AN, Roque DM, Siegel E, et al. Randomized Phase II Trial of Carboplatin-Paclitaxel Compared with Carboplatin-Paclitaxel-Trastuzumab in Advanced (Stage III-IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis[J]. Clin Cancer Res, 2020, 26(15):3928-3935. doi: 10.1158/1078-0432.CCR-20-0953. doi: 10.1158/1078-0432.CCR-20-0953
[16]	Nicoletti R, Lopez S, Bellone S, et al. T-DM1, a novel antibody-drug conjugate, is highly effective against uterine and ovarian carcinosarcomas overexpressing HER2[J]. Clin Exp Metastasis, 2015, 32(1):29-38. doi: 10.1007/s10585-014-9688-8. doi: 10.1007/s10585-014-9688-8
[17]	Black J, Menderes G, Bellone S, et al. SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody-Drug Conjugate, Shows Antitumor Activity in Uterine Serous Carcinoma with HER2/Neu Expression[J]. Mol Cancer Ther, 2016, 15(8):1900-1909. doi: 10.1158/1535-7163.MCT-16-0163. doi: 10.1158/1535-7163.MCT-16-0163
[18]	Schwab CL, Bellone S, English DP, et al. Afatinib demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro and in vivo[J]. Br J Cancer, 2014, 111(9):1750-1756. doi: 10.1038/bjc.2014.519. doi: 10.1038/bjc.2014.519
[19]	El-Sahwi K, Bellone S, Cocco E, et al. In vitro activity of pertuzumab in combination with trastuzumab in uterine serous papillary adenocarcinoma[J]. Br J Cancer, 2010, 102(1):134-143. doi: 10.1038/sj.bjc.6605448. doi: 10.1038/sj.bjc.6605448
[20]	Eso Y, Shimizu T, Takeda H, et al. Microsatellite instability and immune checkpoint inhibitors: toward precision medicine against gastrointestinal and hepatobiliary cancers[J]. J Gastroenterol, 2020, 55(1):15-26. doi: 10.1007/s00535-019-01620-7. doi: 10.1007/s00535-019-01620-7
[21]	Konstantinopoulos PA, Luo W, Liu JF, et al. Phase II Study of Avelumab in Patients With Mismatch Repair Deficient and Mismatch Repair Proficient Recurrent/Persistent Endometrial Cancer[J]. J Clin Oncol, 2019, 37(30):2786-2794. doi: 10.1200/JCO.19.01021. doi: 10.1200/JCO.19.01021 pmid: 31461377
[22]	Makker V, Taylor MH, Aghajanian C, et al. Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer[J]. J Clin Oncol, 2020, 38(26):2981-2992. doi: 10.1200/JCO.19.02627. doi: 10.1200/JCO.19.02627 pmid: 32167863
[23]	Suyama K, Iwase H. Lenvatinib: A Promising Molecular Targeted Agent for Multiple Cancers[J]. Cancer Control, 2018, 25(1):1073274818789361. doi: 10.1177/1073274818789361. doi: 10.1177/1073274818789361
[24]	Vanhaesebroeck B, Perry M, Brown JR, et al. PI3K inhibitors are finally coming of age[J]. Nat Rev Drug Discov, 2021, 20(10):741-769. doi: 10.1038/s41573-021-00209-1. doi: 10.1038/s41573-021-00209-1 pmid: 34127844
[25]	Weigelt B, Warne PH, Lambros MB, et al. PI3K pathway dependencies in endometrioid endometrial cancer cell lines[J]. Clin Cancer Res, 2013, 19(13):3533-3544. doi: 10.1158/1078-0432.CCR-12-3815. doi: 10.1158/1078-0432.CCR-12-3815 pmid: 23674493
[26]	Slomovitz BM, Jiang Y, Yates MS, et al. Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma[J]. J Clin Oncol, 2015, 33(8):930-936. doi: 10.1200/JCO.2014.58.3401. doi: 10.1200/JCO.2014.58.3401 pmid: 25624430
[27]	Lopez S, Cocco E, Black J, et al. Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo[J]. Mol Cancer Ther, 2015, 14(11):2519-2526. doi: 10.1158/1535-7163.MCT-15-0383. doi: 10.1158/1535-7163.MCT-15-0383
[28]	Wallbillich JJ, Morris RT, Ali-Fehmi R. Comparing mutation frequencies for homologous recombination genes in uterine serous and high-grade serous ovarian carcinomas: A case for homologous recombination deficiency testing in uterine serous carcinoma[J]. Gynecol Oncol, 2020, 159(2):381-386. doi: 10.1016/j.ygyno.2020.08.012. doi: 10.1016/j.ygyno.2020.08.012 pmid: 32900500
[29]	Liu JF, Xiong N, Campos SM, et al. Phase II Study of the WEE1 Inhibitor Adavosertib in Recurrent Uterine Serous Carcinoma[J]. J Clin Oncol, 2021, 39(14):1531-1539. doi: 10.1200/JCO.20.03167. doi: 10.1200/JCO.20.03167
[30]	Kong A, Mehanna H. WEE1 Inhibitor: Clinical Development[J]. Curr Oncol Rep, 2021, 23(9):107. doi: 10.1007/s11912-021-01098-8. doi: 10.1007/s11912-021-01098-8