Cancer Genetics and Epigenetics 2024, Vol.12, No.5, 294-305 http://medscipublisher.com/index.php/cge 301 5.4 Tumor Heterogeneity in Ovarian Cancer and Resistance to Gene Editing Therapies Ovarian cancer is characterized by significant intra-tumor heterogeneity, which complicates the effectiveness of gene editing therapies. Tumor heterogeneity refers to the presence of genetically distinct subclones within the same tumor, which can lead to varying responses to treatment. Some tumor cells may harbor mutations that make them resistant to gene editing interventions, causing therapeutic failure and disease recurrence. In high-grade serous ovarian cancer (HGSOC), the development of chemoresistant subclones during treatment has been documented, with these subclones contributing to tumor relapse and poor prognosis (Schwarz et al., 2015). Similarly, clonal evolution in response to therapies like CRISPR-mediated knockout of oncogenes can lead to the emergence of resistant populations that continue to drive disease progression. Addressing this challenge requires combination therapies that target multiple pathways or distinct subclones within the tumor to prevent resistance. 6 Future Directions in Ovarian Cancer Gene Editing 6.1 Combining gene editing with other cancer therapies Gene editing technologies, particularly CRISPR-Cas9, are poised to revolutionize the treatment of ovarian cancer. The future of these technologies includes integrating gene editing with other cancer therapies, tailoring treatments to individual patients, advancing early detection and prevention strategies, and exploring the potential of epigenetic modifications. Each direction represents a major leap toward more effective and personalized ovarian cancer treatments. Combining gene editing with existing cancer therapies holds great promise in ovarian cancer treatment. Traditional treatments, like chemotherapy and targeted therapies such as PARP inhibitors, often face the challenge of resistance. Gene editing can address this by targeting specific mutations or pathways that contribute to resistance. For example, editing genes like BRCA1 and BRCA2 can enhance the effectiveness of PARP inhibitors by exploiting synthetic lethality. Research has shown that using CRISPR-Cas9 to target these mutations in combination with PARP inhibitors significantly improves therapeutic outcomes (Luo et al., 2021). Immunotherapies, which have revolutionized cancer treatment in recent years, also stand to benefit from gene editing. By modifying immune cells like T-cells or NK cells using CRISPR, their ability to target and eliminate ovarian cancer cells can be enhanced, offering a promising therapeutic avenue. As gene editing technologies evolve, combination approaches that integrate these therapies with traditional methods are expected to improve treatment responses, overcome resistance, and offer personalized options for patients with ovarian cancer. 6.2 Precision medicine: tailoring gene editing to individual patients Precision medicine is an emerging approach in cancer treatment, and gene editing plays a crucial role in its advancement. In ovarian cancer, tailoring treatment based on an individual's genetic profile is becoming increasingly feasible due to advances in sequencing technologies that allow for detailed molecular characterization of tumors. Gene editing can be applied to correct or target specific mutations, such as in TP53, KRAS, and BRCA, which drive cancer progression. The use of CRISPR in precision medicine enables the development of highly personalized treatment strategies aimed at correcting these mutations or enhancing the effectiveness of targeted therapies (Aust et al., 2019). Precision medicine tumor boards, which assess individual patient mutations and recommend personalized treatments, are becoming more common in clinical practice. Studies have shown that personalized treatment plans based on molecular profiles lead to better outcomes, particularly in advanced ovarian cancer cases. Gene editing has the potential to become a cornerstone of these personalized approaches, providing targeted interventions with fewer side effects compared to standard therapies. This precision, combined with the ability to correct specific genetic abnormalities, offers a pathway to more effective treatments that are tailored to the unique genetic landscape of each patient’s cancer. 6.3 Gene editing for early detection and prevention Gene editing technologies offer exciting possibilities for the early detection and prevention of ovarian cancer. One potential application is the use of CRISPR-based diagnostic tools to detect early genetic changes associated with
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