CGE2025v13n2

Cancer Genetics and Epigenetics, 2025, Vol.13, No.2, 50-61 http://medscipublisher.com/index.php/cge 51 detection and disease diagnosis of advanced ovarian cancer. It will study the shortcomings of traditional chemotherapy and surgical treatment, and explore new directions for personalized and precise treatment, such as genetic testing, customized surgical plans, and new drug delivery techniques. Clarifying these methods can influence the treatment outcome of patients and the future development trend of personalized treatment. 2 Molecular Biological Characteristics of Advanced Ovarian Cancer 2.1 Common gene mutations In the pathogenesis of advanced ovarian cancer, gene mutations play a key role, among which the mutations of the two genes BRCA1 and BRCA2 are particularly important. These gene mutations can cause functional defects in homologous recombination repair, making it difficult for cells to repair broken double-stranded DNA, and also making tumors more sensitive to targeted therapeutic drugs such as PARP inhibitors (Figure 1) (Lheureux et al., 2019; Colombo et al., 2024). High-grade serous ovarian cancer is the most common type. This type of cancer often has TP53 gene mutations, which can lead to genetic instability and cause the tumor to deteriorate continuously (Hollis and Gourley, 2016; Lheureux et al., 2019; Hollis, 2023). Figure 1 Illustration of clinical features associated with BRCA1/2 mutations in advanced high-grade serous ovarian cancer: advanced disease at presentation and rapid progression (Adopted from Colombo et al., 2024) Image caption: C: advanced ovarian cancer diagnosed in a 40 year-old patient with a germline BRCA1 gene mutation; Figure 1 C1, C2, C3 and C4: CT-scan, PET-scan and diagnostic laparoscopy revealed an extended peritoneal carcinomatosis despites the patient had undergone prophylactic adnexectomy 4 months earlier; During this prophylactic surgery, no extension to the peritoneum was observed with normal adnexa on histological examination; Patient was treated with neoadjuvant chemotherapy and interval cytoreductive surgery. Patient is still receiving maintenance treatment with olaparib and bevacizumab; D: rapid progression of a peritoneal carcinomatosis in a 35-year-old patient with a BRCA1 germline mutation; Figs. D1, D2, D3 and D4: Significant progression of the ovarian mass and peritoneal implants was observed between initial MRI and complementary CT-scan MRI, even though these examinations are only 15 days apart; Patient was treated with neoadjuvant chemotherapy and interval cytoreductive surgery; Patient is still receiving maintenance treatment with olaparib and bevacizumab (Adopted from Colombo et al., 2024) The situation of BRCA1/2 gene mutations and homologous recombination for repairing functional defects not only affects the therapeutic effect, but also is related to the surgical plan and the recovery of patients (Lheureux et al., 2019; Garsed et al., 2022; Colombo et al., 2024). For instance, for patients carrying BRCA1/2 gene mutations, maintenance treatment with PARP inhibitors may have a better effect, and the growth characteristics of their tumors are also different compared with those without these mutations (Colombo et al., 2024; Garsed et al., 2022). Understanding these genetic changes is crucial for formulating treatment plans suitable for each patient and improving the treatment effect (Hollis and Gourley, 2016; Lheureux et al., 2019; Colombo et al., 2024). 2.2 Clinical significance of different molecular subtypes Ovarian cancer is not a single disease. It encompasses a variety of different tissue types and molecular types, and the manifestations and patient recovery conditions of each type are different (Rojas et al., 2016; Hollis and

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