Molecular genetic markers of ovarian cancer tumor cells and their microenvironment, study methods, and clinical value: A review
- Authors: Kalfa M.A.1, Golovkin I.O.1, Lazarev A.E.1, Golubinskaya L.P.1, Gritskevich O.Y.1, Zyablitskaya E.Y.1
-
Affiliations:
- Vernadsky Crimean Federal University
- Issue: Vol 25, No 3 (2023)
- Pages: 308-312
- Section: CLINICAL ONCOLOGY
- URL: https://journals.rcsi.science/1815-1434/article/view/148895
- DOI: https://doi.org/10.26442/18151434.2023.3.202422
- ID: 148895
Cite item
Full Text
Abstract
Ovarian cancer (OC) is a common malignancy of the female reproductive system. In most patients, OC is diagnosed in the later stages, leading to an abysmal prognosis. The standard treatment for OC is surgery and chemotherapy; however, relapse often occurs after treatment, especially in patients with advanced disease. New therapeutic options based on advances in tumor genetics and molecular biology are needed to improve treatment outcomes. Manipulations with genes and the proteins they express, affecting oncogenesis and treatment resistance, seem promising, and proteins and gene fragments identified using molecular methods become valuable markers in the supportive pharmacodiagnosis and tailoring of complex therapy. This article describes the research achievements in genetic markers in OC.
Keywords
Full Text
##article.viewOnOriginalSite##About the authors
Margarita A. Kalfa
Vernadsky Crimean Federal University
Email: rita.kalfa@mail.ru
ORCID iD: 0000-0002-7179-3402
cand. sci. (med.)
Russian Federation, SimferopolIlya O. Golovkin
Vernadsky Crimean Federal University
Email: golovkin.io.1996@gmail.com
ORCID iD: 0000-0002-3578-5130
res. assist.
Russian Federation, SimferopolArtem E. Lazarev
Vernadsky Crimean Federal University
Email: artik.lazarev@gmail.com
ORCID iD: 0000-0003-2684-3834
аssistant
Russian Federation, SimferopolLena P. Golubinskaya
Vernadsky Crimean Federal University
Email: missive@mail.ru
ORCID iD: 0000-0003-3917-924X
d. sci. (med.)
Russian Federation, SimferopolOlga Yu. Gritskevich
Vernadsky Crimean Federal University
Email: editor@omnidoctor.ru
ORCID iD: 0000-0002-3556-1399
аssistant
Russian Federation, SimferopolEvgenia Yu. Zyablitskaya
Vernadsky Crimean Federal University
Author for correspondence.
Email: evgu79@mail.ru
ORCID iD: 0000-0001-8216-4196
d. sci. (med.)
Russian Federation, SimferopolReferences
- Kurman RJ. WHO Classification of tumours of female reproductive organs. Lyon: International Agency for Research on Cancer, 2014.
- Leung DTH, Fuller PJ, Chu S. Impact of FOXL2 mutations on signaling in ovarian granulosa cell tumors. Int J Biochem Cell Biol. 2016;72:51-4. doi: 10.1016/j.biocel.2016.01.003
- Heravi-Moussavi A, Anglesio MS, Cheng SW, et al. Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers. N Engl J Med. 2012;366(3):234-42. doi: 10.1056/NEJMoa1102903
- Maeda D, Shibahara J, Sakuma T, et al. β-catenin (CTNNB1) S33C mutation in ovarian microcystic stromal tumors. Am J Surg Pathol. 2011;35(10):1429-40. doi: 10.1097/PAS.0b013e31822d6c71
- Jelinic P, Mueller JJ, Olvera N, et al. Recurrent SMARCA4 mutations in small cell carcinoma of the ovary. Nat Genet. 2014;46(5):424-6. doi: 10.1038/ng.2922
- Herzog TJ. Recurrent ovarian cancer. Clin Cancer Res. 2004;10(22):7439-49. doi: 10.1158/1078-0432.CCR-04-0683
- Herzog TJ, Pothuri B. Ovarian cancer: A focus on management of recurrent disease. Nat Rev Clin Oncol. 2006;3(11):604-11. doi: 10.1038/ncponc0637
- Хансон К.П., Имянитов Е.Н. Молекулярная генетика рака яичников. Практическая онкология. 2000;1(4):3-6 [Khanson KP, Imianitov EN. Molekuliarnaia genetika raka iaichnikov. Prakticheskaia Onkologiia. 2000;1(4):3-6 (in Russian)].
- Хохлова С.В., Горбунова В.А., Любченко Л.Н., Имянитов Е.Н. BRCA-ассоциированный рак яичников (опыт отделения химиотерапии ФГБУ «РОНЦ им. Н.Н. Блохина» Минздрава России). Современная Онкология. 2016;18(1):37-44 [Khokhlova SV, Gorbunova VA, Lyubchenko LN, Imyanitov EN. BRCA-associated ovarian cancer (the experience of the Chemotherapy Department in N.N. Blokhin Russian Cancer Research Center of the Ministry of Health of Russia). Journal of Modern Oncology. 2016;18(1):37-44 (in Russian)].
- Lu H, Li S, Black MH, et al. Association of breast and ovarian cancers with predisposition genes identified by large-scale sequencing. JAMA Oncol. 2019;5(1):51-7. doi: 10.1001/jamaoncol.2018.2956
- Laurini E, Marson D, Fermeglia A, et al. Role of Rad51 and DNA repair in cancer: A molecular perspective. Pharmacol Ther. 2020;208:107492. doi: 10.1016/j.pharmthera.2020.107492
- Chun J, Buechelmaier ES, Powell SN. Rad51 paralog complexes BCDX2 and CX3 act at different stages in the BRCA1-BRCA2-dependent homologous recombination pathway. Mol Cell Biol. 2013;33(2):387-95. doi: 10.1128/MCB.00465-12
- Prakash R, Zhang Y, Feng W, Jasin M. Homologous recombination and human health: The roles of BRCA1, BRCA2, and associated proteins. Cold Spring Harb Perspect Biol. 2015;7(4):a016600. doi: 10.1101/cshperspect.a016600
- Sullivan MR, Bernstein KA. RAD-ical new insights into RAD51 regulation. Genes (Basel). 2018;9(12):629. doi: 10.3390/genes9120629
- Orhan E, Velazquez C, Tabet I, et al. Regulation of RAD51 at the transcriptional and functional levels: What prospects for cancer therapy? Cancers (Basel). 2021;13(12):2930. doi: 10.3390/cancers13122930
- Grundy MK, Buckanovich RJ, Bernstein KA. Regulation and pharmacological targeting of RAD51 in cancer. NAR Cancer. 2020;2(3):zcaa024. doi: 10.1093/narcan/zcaa024
- Feng Y, Wang D, Xiong L, et al. Predictive value of RAD51 on the survival and drug responsiveness of ovarian cancer. Cancer Cell Int. 2021;21(1):249. doi: 10.1186/s12935-021-01953-5
- Hoppe MM, Jaynes P, Wardyn JD, et al. Quantitative imaging of RAD51 expression as a marker of platinum resistance in ovarian cancer. EMBO Mol Med. 2021;13(5):e13366. doi: 10.15252/emmm.202013366
- Guffanti F, Alvisi MF, Anastasia A, et al. Basal expression of RAD51 foci predicts olaparib response in patient-derived ovarian cancer xenografts. Br J Cancer. 2022;126(1):120-8. doi: 10.1038/s41416-021-01609-1
- Suszynska M, Ratajska M, Kozlowski P. BRIP1, RAD51C, and RAD51D mutations are associated with high susceptibility to ovarian cancer: mutation prevalence and precise risk estimates based on a pooled analysis of ~30,000 cases. J Ovarian Res. 2020;13(1):50. doi: 10.1186/s13048-020-00654-3
- Meindl A, Hellebrand H, Wiek C, et al. Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene. Nat Genet. 2010;42(5):410-4. doi: 10.1038/ng.569
- Pelttari LM, Heikkinen T, Thompson D, et al. RAD51C is a susceptibility gene for ovarian cancer. Hum Mol Genet. 2011;20(16):3278-88. doi: 10.1093/hmg/ddr229
- Thompson ER, Boyle SE, Johnson J, et al. Analysis of RAD51C germline mutations in high-risk breast and ovarian cancer families and ovarian cancer patients. Hum Mutat. 2012;33(1):95-9. doi: 10.1002/humu.21625
- Yao H, Li N, Yuan H. Clinical characteristics and survival analysis of Chinese ovarian cancer patients with RAD51D germline mutations. BMC Cancer. 2022;22(1):1337. doi: 10.1186/s12885-022-10456-z
- Rubin SC, Finstad CL, Federici MG, et al. Prevalence and significance of HER-2/neu expression in early epithelial ovarian cancer. Cancer. 1994;73(5):1456-9. doi: 10.1002/1097-0142(19940301)73:5<1456::aid-cncr2820730522>3.0.co;2-l
- Luo H, Xu X, Ye M, et al. The prognostic value of HER2 in ovarian cancer: A meta-analysis of observational studies. PLoS One. 2018;13(1):e0191972. doi: 10.1371/journal.pone.0191972
- Swain SM, Clark E, Baselga J. Treatment of HER2-positive metastatic breast cancer. N Engl J Med. 2015;372(20):1964-5. doi: 10.1056/NEJMc1503446
- Bookman MA, Darcy KM, Clarke-Pearson D, et al. Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: A phase II trial of the Gynecologic Oncology Group. J Clin Oncol. 2003;21(2):283-90. doi: 10.1200/JCO.2003.10.104
- Satpathy M, Wang L, Zielinski RJ, et al. Targeted drug delivery and image-guided therapy of heterogeneous ovarian cancer using HER2-targeted theranostic nanoparticles. Theranostics. 2019;9(3):778-95. doi: 10.7150/thno.29964
- Kupryjańczyk J, Madry R, Plisiecka-Hałasa J, et al. TP53 status determines clinical significance of ERBB2 expression in ovarian cancer. Br J Cancer. 2004;91(11):1916-23. doi: 10.1038/sj.bjc.6602238
- Groothuizen FS, Sixma TK. The conserved molecular machinery in DNA mismatch repair enzyme structures. DNA Repair (Amst). 2016;38:14-23. doi: 10.1016/j.dnarep.2015.11.012
- Amaral-Silva GK, Martins MD, Pontes HA, et al. Mismatch repair system proteins in oral benign and malignant lesions. J Oral Pathol Med. 2017;46(4):241-5. doi: 10.1111/jop.12484
- Gupta D, Heinen CD. The mismatch repair-dependent DNA damage response: Mechanisms and implications. DNA Repair (Amst). 2019;78:60-9. doi: 10.1016/j.dnarep.2019.03.009
- Erie DA, Weninger KR. Single molecule studies of DNA mismatch repair. DNA Repair (Amst). 2014;20:71-81. doi: 10.1016/j.dnarep.2014.03.007
- Cilona M, Locatello LG, Novelli L, Gallo O. The mismatch repair system (MMR) in head and neck carcinogenesis and its role in modulating the response to immunotherapy: A critical review. Cancers. 2020;12(10):3006. doi: 10.3390/cancers12103006
- Loeb LA. A mutator phenotype in cancer. Cancer Res. 2001;61(8):3230-9. PMID: 11309271
- Pećina-Šlaus N, Kafka A, Salamon I, Bukovac A. Mismatch repair pathway, genome stability and cancer. Front Mol Biosci. 2020;7:122. doi: 10.3389/fmolb.2020.00122
- Rambau PF, Duggan MA, Ghatage P, et al. Significant frequency of MSH2/MSH6 abnormality in ovarian endometrioid carcinoma supports histotype-specific Lynch syndrome screening in ovarian carcinomas. Histopathology. 2016;69(2):288-97. doi: 10.1111/his.12934
- Helder-Woolderink JM, Blok EA, Vasen HF, et al. Ovarian cancer in Lynch syndrome: A systematic review. Eur J Cancer. 2016;55:65-73. doi: 10.1016/j.ejca.2015.12.005
- Samimi G, Fink D, Varki NM, et al. Analysis of MLH1 and MSH2 expression in ovarian cancer before and after platinum drug-based chemotherapy. Clin Cancer Res. 2000;6(4):1415-21. PMID: 10778972
- Xiao X, Melton DW, Gourley C. Mismatch repair deficiency in ovarian cancer – molecular characteristics and clinical implications. Gynecol Oncol. 2014;132(2):506-12. doi: 10.1016/j.ygyno.2013.12.003
- Балдуева И.А., Нехаева Т.Л., Проценко С.А., и др. Дендритноклеточные вакцины в иммунотерапии больных солидными опухолями. СПб.: НМИЦ онкологии им. Н.Н. Петрова, 2020 [Baldueva IA, Nekhaeva TL, Protsenko SA, et al. Dendritnokletochnye vaktsiny v immunoterapii bol'nykh solidnymi opukholiami. Saint Peterburg: NMITs onkologii im. N.N. Petrova, 2020 (in Russian)].
- Гуторов С.Л., Давыдова И.Ю., Новикова Е.Г., и др. Практические рекомендации по лекарственному лечению злокачественных неэпителиальных опухолей яичников. Злокачественные опухоли. 2022;12(3s2-1):212-28 [Gutorov SL, Davydova IIu, Novikova EG, et al. Prakticheskie rekomendatsii po lekarstvennomu lecheniiu zlokachestvennykh neepitelial'nykh opukholei iaichnikov. Zlokachestvennye Opukholi. 2022;12(3s2-1):212-28 (in Russian)]. doi: 10.18027/2224-5057-2022-12-3s2-212-228
- Давыдова И.Ю., Валиев Р.К., Карселадзе А.И., и др. Практические рекомендации по лечению пограничных опухолей яичников. Злокачественные опухоли. 2022;12(3s2-1):229-39 [Davydova IIu, Valiev RK, Karseladze AI, et al. Prakticheskie rekomendatsii po lecheniiu pogranichnykh opukholei iaichnikov. Zlokachestvennye Opukholi. 2022;12(3s2-1):229-39 (in Russian)]. doi: 10.18027/2224-5057-2022-12-3s2-229-239
- Тюлядина А.С., Коломиец Л.А., Морзов К.Ю., и др. Практические рекомендации по лекарственному лечению рака яичников, первичного рака брюшины и рака маточных труб. Злокачественные опухоли. 2022;12(3s2-1):198-211 [Tiuliadina AS, Kolomiets LA, Morzov KIu, et al. Prakticheskie rekomendatsii po lekarstvennomu lecheniiu raka iaichnikov, pervichnogo raka briushiny i raka matochnykh trub. Zlokachestvennye Opukholi. 2022;12(3s2-1):198-211 (in Russian)]. doi: 10.18027/2224-5057-2022-12-3s2-198-211
- D'Aloia MM, Zizzari IG, Sacchetti B, et al. CAR-T cells: The long and winding road to solid tumors. Cell Death Dis. 2018;9(3):282. doi: 10.1038/s41419-018-0278-6
- Macpherson AM, Barry SC, Ricciardelli C, Oehler MK. Epithelial ovarian cancer and the immune system: Biology, interactions, challenges and potential advances for immunotherapy. J Clin Med. 2020;9(9):2967. doi: 10.3390/jcm9092967
- Guo ZS. The 2018 Nobel Prize in medicine goes to cancer immunotherapy (editorial for BMC cancer). BMC Cancer. 2018;18(1):1086. doi: 10.1186/s12885-018-5020-3
- Dumauthioz N, Labiano S, Romero P. Tumor resident memory T cells: New players in immune surveillance and therapy. Front Immunol. 2018;9:2076. doi: 10.3389/fimmu.2018.02076