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INTERNATIONAL CONGRESS OF

CancerGenetics

• Stem Cells for the Treatment of Ovarian Cancer Review article

• katayoun Aliyari,^1,* Haniye fayezi,²
  1. M.sc of Molecular genetics dr.aliyaripathobiolab,Borujerd Iran.
  2. M.sc of Pathogenic Microbes Islamic Azad University North Tehran Branch,Tehran Iran.
  
  
  
• Introduction: Ovarian cancer is one of the leading causes of mortality among women with benign gynecological diseases, particularly occurring in postmenopausal women. It ranks fifth after lung, breast, colorectal, and pancreatic cancers and has a significant impact on overall health. Ovarian cancer encompasses a diverse group of diseases that arise from various tissues of the female reproductive organs. Early-stage ovarian cancer is often undetectable, leading to diagnosis at more advanced stages. The prognosis and treatment of ovarian cancer patients depend on the duration of the disease following cytoreductive surgery. The repeated rupture of the epithelial tissue during ovulation may be responsible for the different types of ovarian cancer, a hypothesis that has emerged from pathological samples obtained from surgeries showing that epithelial tissue in the fallopian tubes serves as a source for various forms of ovarian cancer. It is presumed that the origin of cancer stem cells (CSCs) in ovarian cancer is due to the effects of DNA damage from ovulation and wounding, which affects quiescent stem cells located in the surface epithelial tissue of the ovary. It has been suggested that the presence of common genes in the surface epithelial tissue of the ovary, which are overactive in ovarian cancer, plays a role in the development of this cancer, establishing a connection between ovulation and the development of ovarian cancer.
• Methods: The standard treatment strategy for ovarian cancer involves surgical resection of the tumor, followed by chemotherapy based on taxanes and platinum compounds. This treatment strategy results in an 80% partial response rate and a 40-60% complete response rate, with a 5-year survival rate of approximately 30%. However, the recurrence rate of the disease remains high at 70%. This statistic suggests that while most ovarian cancers are initially sensitive to chemotherapy, the significant chance of recurrence indicates that some cancer cells are not eliminated by the chemotherapeutic agents and/or can regenerate after exposure to these agents. The efficacy of individual drugs against ovarian cancer stem cells (CSCs) is limited due to their heterogeneity, and targeting ovarian CSCs has proven to be a considerable challenge for researchers. Furthermore, the current first-line treatment for ovarian cancer involves a combination of paclitaxel and carboplatin, which has been associated with an increased incidence of chemoresistance. While combining multiple drugs may be used to target CSCs, it also raises the risk of toxicity, as CSCs may possess characteristics similar to normal cells. This characteristic of CSCs indicates that specific tumor cells perform functions akin to those of normal stem cells. Given the significant success in developing antibody-drug conjugates, specific therapies have been developed that can target biomarkers of ovarian CSCs and improve oncogenic outcomes and patient survival. Numerous cell surface markers, particularly CD117, CD24, CD44, EpCAM, and CD133, have been reported for the isolation of potential CSCs. EpCAM is increasingly expressed in various tumor types, and its reduced expression may lead to the loss of cell-cell adhesion capabilities and promote epithelial-to-mesenchymal transition. Catumaxomab is a monoclonal antibody against EpCAM that is tri-functional, engaging three different cell types: tumor cells, immune effector cells, and accessory cells. Additionally, Lin28 and Oct4 can also serve as targeted therapies for pluripotency in ovarian cancer.
• Results: The scientific studies presented in this chapter indicate that the presence of cancer stem cells (CSCs) in ovarian tumors is responsible for the initiation of ovarian cancer pathogenesis and tumor formation. Furthermore, these CSCs also contribute to increased chemotherapy resistance in ovarian tumors, along with the generation of more non-tumorigenic differentiated cells. To eliminate these CSCs, understanding the biology and functional role of these CSCs in ovarian tumors is quite complex. Recent advancements in identifying new antibody-drug conjugates (ADCs) for targeting these CSCs in ovarian cancers have shown promise in eradicating ovarian CSCs.
• Conclusion: These cells are also known as growth factor receptors of cancer stem cells and exhibit increased expression in ovarian cancer cells, demonstrating significant tumorigenicity in mouse models. They play roles in cellular proliferation, differentiation, adhesion, and apoptosis. CD117-positive cells activate the Wnt/β-catenin pathway, which has a key role in the development of chemotherapy resistance. One study reported that immunohistochemical analysis of 25 patients with advanced ovarian cancer showed that CD117-positive cell expression was detected in up to 40% of patients, and the expression of CD117 was strongly associated with the development of chemotherapy resistance. The use of chemotherapy agents alongside surgery is an effective treatment strategy for reducing tumor volume; however, most patients develop chemotherapy resistance due to the persistence of ovarian cancer stem cells. It has been described that even a small number of cancer stem cells remaining after chemotherapy may increase the likelihood of disease recurrence. Several pathways have been proposed to be involved in the mechanisms related to this resistance, including the inactivation of pro-apoptotic factors, activation of anti-apoptotic factors, and enhancement of survival signals. Based on these mechanisms, understanding the incorrect response of cancer stem cells to chemotherapy may be attributed to factors such as drug flow, tumor dormancy, dormancy of cancer stem cells, enrichment of cancer stem cells during disease progression, glutathione system involvement, and apoptosis.
• Keywords: Ovarian,Treatment,Stem cells,Cancer,Biomarkers of Ovarian