An in-Depth Analysis of Ovarian Cancer: Pathogenesis and Clinical Manifestation

Abstract

Ovarian cancer is characterized by the establishment of tolerance, the recurrence of disease, as well as a poor prognosis. Gene signatures in ovarian cancer cells enable cancer medicine research, therapy, prevention, & management problematic. Notwithstanding advances in tumor puncture surgery, novel combinations regimens, and abdominal radiation, which can provide outstanding reaction times, the bulk of gynecological tumor patients suffer from side effects & relapse. As a consequence, more therapy alternatives for individuals with ovarian cancer must always be studied to minimize side effects and improve progression-free and total response rates. The development of cancer medications is presently undergoing a renaissance in the quest for descriptive and prognostic ovarian cancer biomarkers. Nevertheless, abnormalities in the BRCA2 or BRCA1 genes, a variety of hereditary predispositions, unexplained onset and progression, molecular tumor diversity, and illness staging can all compromise the responsiveness and accuracy of such indicators. As a result, current ovarian cancer treatments must be supplemented with broad-spectrum & customized targeted therapeutic approaches. The objective of this review is to highlight recent contributions to the knowledge of the interrelations between selected ovarian tumor markers, various perception signs, and biochemical and molecular signaling processes, as well as one’s interpretation of much more targeted and effective treatment interventions.

Keywords

Ovarian Cancer - Prognosis - Gynecological Tumor - BRCA2 - and BRCA1

Publikationsverlauf

Eingereicht: 01. März 2022

Angenommen: 23. Mai 2022

Artikel online veröffentlicht:
27. Juni 2022

• References:

• 1 Banerjee S, Gore M. The Future of Targeted Therapies in Ovarian Cancer. Oncologist 2009; 14: 706-716
• 2 Bast RC, Mills GB. Personalizing therapy for ovarian cancer: BRCAness and beyond. J Clin Oncol 2010; 28: 3545-3548
• 3 Guarneri V, Piacentini F, Barbieri E. et al. Achievements and unmet needs in the management of advanced ovarian cancer. Gynecol Oncol 2010; 117: 152-158
• 4 Itamochi H. Targeted therapies in epithelial ovarian cancer: Molecular mechanisms of action. World J Biol Chem 2010; 1: 220
• 5 Bray F, Jemal A, Grey N. et al. Global cancer transitions according to the Human Development Index (2008–2030): a population-based study. Lancet Oncol 2012; 13: 790-801
• 6 Siegel R, Ward E, Brawley O. et al. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin 2011; 61: 212-236
• 7 Anglesio MS, George J, Kulbe H. et al. IL6-STAT3-HIF signaling and therapeutic response to the angiogenesis inhibitor sunitinib in ovarian clear cell cancer. Clin Cancer Res 2011; 17: 2538-2548
• 8 Farra R, Maruna M, Perrone F. et al. Strategies for Delivery of siRNAs to Ovarian Cancer Cells. Pharmaceutics 2019; 11: 562
• 9 Annunziata CM, Kohn EC. Is there a genomic basis for primary chemoresistance in ovarian cancer?. Gynecol Oncol 2003; 90: 1-2
• 10 Barrès V, Ouellet V, Lafontaine J. et al. An essential role for Ran GTPase in epithelial ovarian cancer cell survival. Mol Cancer 2010; 9: 281
• 11 Creekmore AL, Silkworth WT, Cimini D. et al. Changes in Gene Expression and Cellular Architecture in an Ovarian Cancer Progression Model. PLoS One 2011; 6: e17688
• 12 Gangemi R, Paleari L, Orengo A. et al. Cancer stem cells: a new paradigm for understanding tumor growth and progression and drug resistance. Curr Med Chem 2009; 16: 1688-1703
• 13 Gómez-Raposo C, Mendiola M, Barriuso J. et al. Molecular characterization of ovarian cancer by gene-expression profiling. Gynecol Oncol 2010; 118: 88-92
• 14 Zahedi P, De Souza R, Huynh L. et al. Combination drug delivery strategy for the treatment of multidrug resistant ovarian cancer. Mol Pharm 2011; 8: 260-269
• 15 Liu HG, Chen C, Yang H. et al. Cancer stem cell subsets and their relationships. J Transl Med 2011; 9: 1-9
• 16 Halon A, Materna V, Drag-Zalesinska M. et al. Estrogen receptor alpha expression in ovarian cancer predicts longer overall survival. Pathol Oncol Res 2011; 17: 511-518
• 17 Deraco M, Baratti D, Laterza B. et al. Advanced cytoreduction as surgical standard of care and hyperthermic intraperitoneal chemotherapy as promising treatment in epithelial ovarian cancer. Eur J Surg Oncol 2011; 37: 4-9
• 18 Colombo N. Optimizing treatment of the partially platinum-sensitive ovarian cancer patient. Futur Oncol 2013; 9: 19-23
• 19 Altomare DA, Hui QW, Skele KL. et al. AKT and mTOR phosphorylation is frequently detected in ovarian cancer and can be targeted to disrupt ovarian tumor cell growth. Oncogene 2004; 23: 5853-5857
• 20 Aletti GD, Eisenhauer EL, Santillan A. et al. Identification of patient groups at highest risk from traditional approach to ovarian cancer treatment. Gynecol Oncol 2011; 120: 23-28
• 21 Pliarchopoulou K, Pectasides D. Epithelial ovarian cancer: focus on targeted therapy. Crit Rev Oncol Hematol 2011; 79: 17-23
• 22 Husseinzadeh N. Status of tumor markers in epithelial ovarian cancer has there been any progress? A review. Gynecol Oncol 2011; 120: 152-157
• 23 Beran TM, Stanton AL, Kwan L. et al. The trajectory of psychological impact in BRCA1/2 genetic testing: does time heal?. Ann Behav Med 2008; 36: 107-116
• 24 Bast RC, Hennessy B, Mills GB. The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer 2009; 9: 415-428
• 25 Hille S, Rein DT, Riffelmann M. et al. Anticancer drugs induce mdr1 gene expression in recurrent ovarian cancer. Anticancer Drugs 2006; 17: 1041-1044
• 26 Hanash SM, Baik CS, Kallioniemi O. Emerging molecular biomarkers – blood-based strategies to detect and monitor cancer. Nat Rev Clin Oncol 2011; 8: 142-150
• 27 Williams TI, Toups KL, Saggese DA. et al. Epithelial ovarian cancer: disease etiology, treatment, detection, and investigational gene, metabolite, and protein biomarkers. J Proteome Res 2007; 6: 2936-2962
• 28 Ardekani AM, Liotta LA, Petricoin EF. Clinical potential of proteomics in the diagnosis of ovarian cancer. Expert Rev Mol Diagn 2002; 2: 312-320
• 29 Njoku K, Chiasserini D, Whetton AD. et al. Proteomic Biomarkers for the Detection of Endometrial Cancer. Cancers (Basel) 2019; 11: 1572-1579
• 30 Fotopoulou C, Richter R, Braicu IE. et al. Clinical outcome of tertiary surgical cytoreduction in patients with recurrent epithelial ovarian cancer. Ann Surg Oncol 2011; 18: 49-57
• 31 Frenel JS, Leux C, Pouplin L. et al. Oxaliplatin-based hyperthermic intraperitoneal chemotherapy in primary or recurrent epithelial ovarian cancer: A pilot study of 31 patients. J Surg Oncol 2011; 103: 10-16
• 32 Wu H-C, Chang D-K, Huang C-T. Targeted therapy for cancer. J Mol Cancer 2006; 2: 57-66
• 33 Elsayed AM, Amero P, Salama SA. et al. Back to the Future: Rethinking the Great Potential of lncRNA S for Optimizing Chemotherapeutic Response in Ovarian Cancer. Cancers (Basel) 2020; 12: 1-35
• 34 Tomasova K, Cumova A, Seborova K. et al. DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome. Cancers (Basel) 2020; 12: 1-37
• 35 Yip L, Kelly L, Shuai Y. et al. MicroRNA Signature Distinguishes the Degree of Aggressiveness of Papillary Thyroid Carcinoma. Ann Surg Oncol 2011; 18: 2041
• 36 Smallridge RC, Marlow LA, Copland JA. Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies. Endocr Relat Cancer 2009; 16: 44
• 37 Sekine M, Enomoto T, Arai M. et al. Correlation between the risk of ovarian cancer and BRCA recurrent pathogenic variants in Japan. J Hum Genet 2022; 2: 1-6
• 38 Aksoy F, Tezcan Unlu H, Cecener G. et al. Identification of CHEK2 germline mutations in BRCA1/2 and PALB2 negative breast and ovarian cancer patients. Hum Hered 2022; 3: 56-62
• 39 Perkhofer L, Gout J, Roger E. et al. DNA damage repair as a target in pancreatic cancer: state-of-the-art and future perspectives. Gut 2021; 70: 606-617
• 40 McMullen M, Madariaga A, Lheureux S. New approaches for targeting platinum-resistant ovarian cancer. Semin Cancer Biol 2021; 77: 167-181
• 41 Xiang J, Zhou L, He Y. et al. LDH-A inhibitors as remedies to enhance the anticancer effects of PARP inhibitors in ovarian cancer cells. Aging (Albany NY) 2021; 13: 25930
• 42 Leber MF, Efferth T. Molecular principles of cancer invasion and metastasis (review). Int J Oncol 2009; 34: 881-895
• 43 Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 2010; 10: 9-22
• 44 Dixon JA, Oliver SCN, Olson JL. et al. VEGF Trap-Eye for the treatment of neovascular age-related macular degeneration. Expert Opin Investig Drugs 2009; 18: 1573-1580
• 45 Moschetta M, Cesca M, Pretto F. et al. Angiogenesis Inhibitors: Implications for Combination with Conventional Therapies. Curr Pharm Des 2011; 16: 3921-3931
• 46 Zirlik K, Duyster J. Anti-Angiogenics: Current Situation and Future Perspectives. Oncol Res Treat 2018; 41: 166-171
• 47 Eskens FA, Verweij J. Principles and Examples of Cancer (Cell) Specific Therapies. In: Textbook of Medical Oncology. Boca Raton: CRC Press; 2009: 53-67
• 48 Pennell NA, Mekhail T. Investigational agents in the management of non-small cell lung cancer. Curr Oncol Rep 2009; 11: 275-284
• 49 Gilbert M, Mousa S, Mousa SA. Current status of anti-vascular endothelial growth factor (VEGF) strategies and future directions. Drugs Future 2008; 33: 515-525
• 50 Li S, Zhang Q, Hong Y. Tumor Vessel Normalization: A Window to Enhancing Cancer Immunotherapy. Technol Cancer Res Treat 2020; 19: 108-119
• 51 Gomperts B, Kramer I, Tatham P. Signalling pathways operated by receptor protein tyrosine kinases. Signal Transduct 2002; 8: 315-374
• 52 Nelson J. Structure and function in cell signalling. 2nd Aufl.. Hoboken: John Wiley & Sons; 2008
• 53 Baron AT, Lafky JM, Boardman CH. et al. Soluble Epidermal Growth Factor Receptor: A Biomarker of Epithelial Ovarian Cancer. Cancer Treat Res 2009; 149: 189-202
• 54 Lafky JM, Wilken JA, Baron AT. et al. Clinical implications of the ErbB/epidermal growth factor (EGF) receptor family and its ligands in ovarian cancer. Biochim Biophys Acta 2008; 1785: 232-265
• 55 Tanaka Y, Terai Y, Tanabe A. et al. Prognostic effect of epidermal growth factor receptor gene mutations and the aberrant phosphorylation of Akt and ERK in ovarian cancer. Cancer Biol Ther 2011; 11: 50-57
• 56 Gordon MS, Matei D, Aghajanian C. et al. Clinical activity of pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in advanced ovarian cancer: potential predictive relationship with tumor HER2 activation status. J Clin Oncol 2006; 24: 4324-4332
• 57 Annunziata CM, Walker AJ, Minasian L. et al. Vandetanib, designed to inhibit VEGFR2 and EGFR signaling, had no clinical activity as monotherapy for recurrent ovarian cancer and no detectable modulation of VEGFR2. Clin Cancer Res 2010; 16: 664-672
• 58 Lichtenberger BM, Tan PK, Niederleithner H. et al. Autocrine VEGF signaling synergizes with EGFR in tumor cells to promote epithelial cancer development. Cell 2010; 140: 268-279
• 59 Barash U, Cohen-Kaplan V, Dowek I. et al. Proteoglycans in health and disease: New concepts for heparanase function in tumor progression and metastasis. FEBS J 2010; 277: 3890-3903
• 60 Tortora G, Bianco R, Daniele G. et al. Overcoming resistance to molecularly targeted anticancer therapies: rational drug combinations based on EGFR and MAPK inhibition for solid tumours and haematologic malignancies. Drug Resist Updat 2007; 10: 100
• 61 Radulescu A, Zorko NA, Yu X. et al. Preclinical Neonatal Rat Studies of Heparin-Binding EGF-Like Growth Factor in Protection of the Intestines From Necrotizing Enterocolitis. Pediatr Res 2009; 65: 437-442
• 62 Chauhan SC, Kumar D, Jaggi M. Mucins in ovarian cancer diagnosis and therapy. J Ovarian Res 2009; 2: 29
• 63 Van Haaften-Day C, Shen Y, Xu F. et al. OVX1, macrophage-colony stimulating factor, and CA-125–II as tumor markers for epithelial ovarian carcinoma: A critical appraisal. Cancer Interdiscip Int J Am Cancer Soc 2001; 92: 2837-2844
• 64 El-Khoueiry AB, Ning Y, Yang D. et al. A phase I first-in-human study of PRI-724 in patients (pts) with advanced solid tumors. J Clin Oncol 2013; 31: 2501-2501
• 65 Espinosa-Sánchez A, Suárez-Martínez E, Sánchez-Díaz L. et al. Therapeutic Targeting of Signaling Pathways Related to Cancer Stemness. Front Oncol 2020; 10: 1533-1541
• 66 Parte SC, Batra SK, Kakar SS. Characterization of stem cell and cancer stem cell populations in ovary and ovarian tumors. J Ovarian Res 2018; 11: 1-16
• 67 Gubbels JAA, Belisle J, Onda M. et al. Mesothelin-MUC16 binding is a high affinity, N-glycan dependent interaction that facilitates peritoneal metastasis of ovarian tumors. Mol Cancer 2006; 5: 50-58
• 68 Rump A, Morikawa Y, Tanaka M. et al. Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion. J Biol Chem 2004; 279: 9190-9198
• 69 Menon KP, Carrillo RA, Zinn K. Development and plasticity of the Drosophila larval neuromuscular junction. Wiley Interdiscip Rev Dev Biol 2013; 2: 647-670
• 70 Qi F, Li A, Inagaki Y. et al. Chinese herbal medicines as adjuvant treatment during chemoor radio-therapy for cancer. Biosci Trends 2010; 4: 108-119
• 71 Manegold P, Lai KKY, Wu Y. et al. Differentiation Therapy Targeting the β-Catenin/CBP Interaction in Pancreatic Cancer. Cancers (Basel) 2018; 10: 95-109
• 72 Moore MJ, Goldstein D, Hamm J. et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007; 25: 1960-1966
• 73 Li Y, Huang W, Huang S. et al. Screening of anti-cancer agent using zebrafish: comparison with the MTT assay. Biochem Biophys Res Commun 2012; 422: 85-90
• 74 Hafeez BB, Fischer JW, Singh A. et al. Plumbagin inhibits prostate carcinogenesis in intact and castrated PTEN knockout mice via targeting PKCε, Stat3 and epithelial to mesenchymal transition markers. Cancer Prev Res (Phila) 2015; 8: 386
• 75 Gowda R, Kardos G, Sharma A. et al. Nanoparticle-Based Celecoxib and Plumbagin for the Synergistic Treatment of Melanoma. Mol Cancer Ther 2017; 16: 440-452
• 76 Sakunrangsit N, Ketchart W. Plumbagin inhibits cancer stem-like cells, angiogenesis and suppresses cell proliferation and invasion by targeting Wnt/β-catenin pathway in endocrine resistant breast cancer. Pharmacol Res 2019; 150: 104525
• 77 Hafeez BB, Zhong W, Fischer JW. et al. Plumbagin, a medicinal plant (Plumbago zeylanica)-derived 1,4-naphthoquinone, inhibits growth and metastasis of human prostate cancer PC-3M-luciferase cells in an orthotopic xenograft mouse model. Mol Oncol 2013; 7: 428-439
• 78 Zhang HY, Zhang PN, Sun H. Aberration of the PI3K/AKT/mTOR signaling in epithelial ovarian cancer and its implication in cisplatin-based chemotherapy. Eur J Obstet Gynecol Reprod Biol 2009; 146: 81-86
• 79 Funk CD, Laferrière C, Ardakani A. Target product profile analysis of COVID-19 vaccines in phase III clinical trials and beyond: an early 2021 perspective. Viruses 2021; 13: 418
• 80 Zhang B, Zou J, Zhang Q. et al. Progress in the Development of Eukaryotic Elongation Factor 2 Kinase (eEF2K) Natural Product and Synthetic Small Molecule Inhibitors for Cancer Chemotherapy. Int J Mol Sci 2021; 22: 1-25
• 81 Van der Vliet A, Dustin CM, Heppner DE. Redox regulation of protein kinase signaling. In: Oxidative Stress: Eustress and Distress. Massachusetts: Academic Press; 2020: 287-313
• 82 Safarzadeh E, Shotorbani SS, Baradaran B. Herbal Medicine as Inducers of Apoptosis in Cancer Treatment. Adv Pharm Bull 2014; 4: 427
• 83 Pu X, Zhang CR, Zhu L. et al. Possible clues for camptothecin biosynthesis from the metabolites in camptothecin-producing plants. Fitoterapia 2019; 134: 113-128
• 84 Guyon L, Lepeltier E, Passirani C. Self-assembly of peptide-based nanostructures: Synthesis and biological activity. Nano Res 2018; 11: 2315-2335
• 85 Palao-Suay R, Gómez-Mascaraque LG, Aguilar MR. et al. Self-assembling polymer systems for advanced treatment of cancer and inflammation. Prog Polym Sci 2016; C: 207-248
• 86 Wang Y, Cheetham AG, Angacian G. et al. Peptide-drug conjugates as effective prodrug strategies for targeted delivery. Adv Drug Deliv Rev 2017; 110–111: 112-126
• 87 Mateti T, Aswath S, Laha A. Recent advances in electrospun allopathic anti-cancerous drug delivery systems. Mater Today Proc 2021; 43: 2864-2867
• 88 Salem M, Rohani S, Gillies ER. Curcumin, a promising anti-cancer therapeutic: a review of its chemical properties, bioactivity and approaches to cancer cell delivery. RSC Adv 2014; 4: 10815-10829
• 89 Watson JL, Hill R, Yaffe PB. et al. Curcumin causes superoxide anion production and p53-independent apoptosis in human colon cancer cells. Cancer Lett 2010; 297: 1-8
• 90 Qin JJ, Li X, Hunt C. et al. Natural products targeting the p53-MDM2 pathway and mutant p53: Recent advances and implications in cancer medicine. Genes Dis 2018; 5: 204-219
• 91 Ali AY, Farrand L, Kim JY. et al. Molecular determinants of ovarian cancer chemoresistance: new insights into an old conundrum. Ann N Y Acad Sci 2012; 1271: 58-67
• 92 Li F, Chen X, Xu B. et al. Curcumin induces p53-independent necrosis in H1299 cells via a mitochondria-associated pathway. Mol Med Rep 2015; 12: 7806-7814
• 93 Shen T, Han XZ, Wang XN. et al. Protective Effects of Dietary Polyphenols in Human Diseases and Mechanisms of Action. In: Nutritional Antioxidant Therapies: Treatments and Perspectives. Cham: Springer; 2017: 307-345
• 94 Rauf A, Imran M, Butt MS. et al. Resveratrol as an anti-cancer agent: A review. Crit Rev Food Sci Nutr 2018; 58: 1428-1447
• 95 Koltai T. Where do we stand with fermented wheat grain extract for cancer treatment: lights and shadow?. Mult Plant 2021; 4: 21-27
• 96 Zayed S. Comparing Effect of Annonaceae & Emetine Nanoparticles on NFĸB p65 Pathway in Tongue Squamous Cell Carcinoma (scc-25). Egypt Dent J 2021; 67: 2181-2191
• 97 Tewari D, Bawari S, Sharma S. et al. Targeting the crosstalk between canonical Wnt/β-catenin and inflammatory signaling cascades: A novel strategy for cancer prevention and therapy. Pharmacol Ther 2021; 227: 107884
• 98 Miller EM, Samec TM, Alexander-Bryant AA. Nanoparticle delivery systems to combat drug resistance in ovarian cancer. Nanomedicine Nanotechnology, Biol Med 2021; 31: 102317
• 99 Dhama K, Chauhan R, Singhal L. Anti-cancer activity of cow urine: current status and future directions. Int J Cow Sci 2005; 1: 1-25
• 100 Chakravarty M, Vora A. Nanotechnology-based antiviral therapeutics. Drug Deliv Transl Res 2020; 11: 748-787
• 101 Jain S, Yadav V, Jain AK. et al. Nutraceuticals: A Revolutionary Approach for Nano Drug Delivery. In: NanoNutraceuticals. Boca Raton: CRC Press; 2018: 1-22
• 102 Préfontaine M, Donovan JT, Powell JL. et al. Treatment of refractory ovarian cancer with 5-fluorouracil and leucovorin. Gynecol Oncol 1996; 61: 249-252
• 103 Cortes J, Perez-García JM, Llombart-Cussac A. et al. Enhancing global access to cancer medicines. CA Cancer J Clin 2020; 70: 105-124
• 104 Waterhouse PM, Wang MB, Lough T. Gene silencing as an adaptive defence against viruses. Nature 2001; 411: 834-842
• 105 Kraft JC, Freeling JP, Wang Z. et al. Emerging research and clinical development trends of liposome and lipid nanoparticle drug delivery systems. J Pharm Sci 2014; 103: 29-52
• 106 Bourquin J, Milosevic A, Hauser D. et al. Biodistribution, Clearance, and Long-Term Fate of Clinically Relevant Nanomaterials. Adv Mater 2018; 30: e1704307-e1704316
• 107 Samuel SM, Varghese E, Kubatka P. et al. Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer. Biomolecules 2019; 9: 846-853
• 108 Xie S, Sun Y, Liu Y. et al. Development of Alectinib-Based PROTACs as Novel Potent Degraders of Anaplastic Lymphoma Kinase (ALK). J Med Chem 2021; 4: 9120-9140