THE IMPACT OF RAD6 EXPRESSION ON CHEMORESISTANT OVARIAN CANCER: A SYSTEMATIC REVIEW
Main Article Content
Chemotherapy is one of the modalities for treating ovarian cancer (OC), which is one of the most common reproductive organ cancers in women worldwide. Overexpression of RAD6 has been identified as a significant factor in chemoresistance in ovarian cancer patients. This systematic review aims to evaluate the relationship between RAD6 overexpression and chemoresistance in ovarian cancer. The databases used include PubMed, ProQuest, Science Direct, and Google Scholar, focusing on articles from the last 10 years. Out of 162 articles retrieved, only 4 met the selection criteria and were used in the analysis. The analysis results indicate that RAD6 overexpression is closely associated with increased resistance to chemotherapeutic agents, particularly platinum. The underlying mechanisms include enhanced DNA damage tolerance, increased proliferation, invasion, and the ability of cancer cells to develop stem-like phenotypes. These findings highlight RAD6 as a potential therapeutic target in preventing chemoresistance in OC. Further research is needed to develop specific RAD6 inhibitors that can be used in combination with conventional chemotherapy to improve treatment response and patient prognosis.
Keywords:
RAD6
OVARIAN CANCER
CHEMORESISTANT
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2. Yang MQ, Elnitski L. A Systems Biology Comparison of Ovarian Cancers Implicates Putative Somatic Driver Mutations through Protein-Protein Interaction Models. Bader JS, editor. PLoS One [Internet]. 2016 Oct 27;11(10):e0163353. Available from: https://dx.plos.org/10.1371/journal.pone.0163353
3. Akter S, Rahman MA, Hasan MN, Akhter H, Noor P, Islam R, et al. Recent Advances in Ovarian Cancer: Therapeutic Strategies, Potential Biomarkers, and Technological Improvements. Cells [Internet]. 2022 Feb 13;11(4):650. Available from: https://www.mdpi.com/2073-4409/11/4/650
4. Arora T, Mullangi S, Vadakekut ES, Lekkala MR. Epithelial Ovarian Cancer [Internet]. StatPearls. 2024 [cited 2024 Sep 24]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK567760/#:~:text=Consequently%2C those with advanced-stage,recommended to undergo neoadjuvant chemotherapy.
5. Li X, Li Z, Ma H, Li X, Zhai H, Li X, et al. Ovarian cancer: Diagnosis and treatment strategies (Review). Oncol Lett [Internet]. 2024 Jul 18;28(3):441. Available from: http://www.spandidos-publications.com/10.3892/ol.2024.14574
6. Garrido MP, Fredes AN, Lobos-González L, Valenzuela-Valderrama M, Vera DB, Romero C. Current Treatments and New Possible Complementary Therapies for Epithelial Ovarian Cancer. Biomedicines [Internet]. 2021 Dec 31;10(1):77. Available from: https://www.mdpi.com/2227-9059/10/1/77
7. Berek JS, Kehoe ST, Kumar L, Friedlander M. Cancer of the ovary, fallopian tube, and peritoneum. Int J Gynecol Obstet [Internet]. 2018 Oct 11;143(S2):59–78. Available from: https://obgyn.onlinelibrary.wiley.com/doi/10.1002/ijgo.12614
8. Nero C, Ciccarone F, Pietragalla A, Duranti S, Daniele G, Salutari V, et al. Ovarian Cancer Treatments Strategy: Focus on PARP Inhibitors and Immune Check Point Inhibitors. Cancers (Basel) [Internet]. 2021 Mar 15;13(6):1298. Available from: https://www.mdpi.com/2072-6694/13/6/1298
9. Dinkins K, Barton W, Wheeler L, Smith HJ, Mythreye K, Arend RC. Targeted therapy in high grade serous ovarian Cancer: A literature review. Gynecol Oncol Reports [Internet]. 2024 Aug;54:101450. Available from: https://linkinghub.elsevier.com /retrieve/pii/S2352578924 001292
10. Vanderpuye VD, Clemenceau JR V., Temin S, Aziz Z, Burke WM, Cevallos NL, et al. Assessment of Adult Women With Ovarian Masses and Treatment of Epithelial Ovarian Cancer: ASCO Resource-Stratified Guideline. JCO Glob Oncol [Internet]. 2021 Dec;(7):1032–66. Available from: https://ascopubs.org/doi/10.1200/GO.21.00085
11. Ghirardi V, Fagotti A, Ansaloni L, Valle M, Roviello F, Sorrentino L, et al. Diagnostic and Therapeutic Pathway of Advanced Ovarian Cancer with Peritoneal Metastases. Cancers (Basel) [Internet]. 2023 Jan 7;15(2):407. Available from: https://www.mdpi.com/2072-6694/15/2/407
12. Sihombing UHM, Purwoto G, Kekalih A, Rustamadji P. RAD6 Overexpression and Ovarian Cancer Chemo-Resistance: Flow Cytometry and Immunohistochemistry. J Oncol [Internet]. 2024 Apr 15;4(1). Available from: https://journalononcology.org/articles/joo-v4-1128.html
13. Clark DW, Mani C, Palle K. RAD6 promotes chemoresistance in ovarian cancer. Mol Cell Oncol [Internet]. 2018 Jan 2;5(1):e1392403. Available from: https://www.tandfonline.com/doi/full/10.1080/23723556.2017.1392403
14. Somasagara RR, Tripathi K, Spencer SM, Clark DW, Barnett R, Bachaboina L, et al. Rad6 upregulation promotes stem cell-like characteristics and platinum resistance in ovarian cancer. Biochem Biophys Res Commun [Internet]. 2016 Jan;469(3):449–55. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0006291X15310032
15. Somasagara RR, Spencer SM, Tripathi K, Clark DW, Mani C, Madeira da Silva L, et al. RAD6 promotes DNA repair and stem cell signaling in ovarian cancer and is a promising therapeutic target to prevent and treat acquired chemoresistance. Oncogene [Internet]. 2017 Nov 30;36(48):6680–90. Available from: https://www.nature.com/articles/onc2017279
16. Sihombing UHM, Andrijono, Purwoto G, Gandamihardja S, Harahap AR, Rustamadji P, et al. Expression of CD44+/CD24-, RAD6 and DDB2 on chemotherapy response in ovarian Cancer: A prospective flow cytometry study. Gynecol Oncol Reports [Internet]. 2022 Aug;42:101005. Available from: https://linkinghub.elsevier.com/retrieve/pii/S2352578922000856
17. Deng Y, Li Y, Wu T, Chen X, Li X, Cai K, et al. RAD6 Positively Affects Tumorigenesis of Esophageal Squamous Cell Carcinoma by Regulating Histone Ubiquitination of CCNB1. Biol Proced Online [Internet]. 2022 Mar 23;24(1):4. Available from: https://biologicalproceduresonline.biomedcentral.com/articles/10.1186/s12575-022-00165-z
18. Do HA, Baek KH. Cellular functions regulated by deubiquitinating enzymes in neurodegenerative diseases. Ageing Res Rev [Internet]. 2021 Aug;69:101367. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1568163721001148
19. Dang F, Nie L, Wei W. Ubiquitin signaling in cell cycle control and tumorigenesis. Cell Death Differ [Internet]. 2021 Feb;28(2):427–38. Available from: https://www.nature.com/articles/s41418-020-00648-0
20. Maddalena F, Lettini G, Esposito F, Landriscina M. RAD6: A new target to overcome platinum resistance in ovarian cancer? Transl Cancer Res. 2017;6(Suppl 9):S1476–9.
