Rotar Ioana Cristina, Bernad Elena, Moraru Liviu, Ivan Viviana, Apostol Adrian, Bernad Sandor Ianos, Muresan Daniel, Mitranovici Melinda-Ildiko
Obstetrics and Gynecology I, Mother and Child Department, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.
Department of Obstetrics and Gynecology, Center for Neuropsychology and Behavioral Medicine, Center for Laparoscopy, Laparoscopic Surgery and In Vitro Fertilization, "Victor Babes" University of Medicine and Pharmacy from Timișoara, 300041 Timișoara, Romania.
Diagnostics (Basel). 2025 Jul 25;15(15):1872. doi: 10.3390/diagnostics15151872.
UNLABELLED: The biggest challenge in cancer therapy is tumor resistance to the classical approach. Thus, research interest has shifted toward the cancer stem cell population (CSC). CSCs are a small subpopulation of cancer cells within tumors with self-renewal, differentiation, and metastasis/malignant potential. They are involved in tumor initiation and development, metastasis, and recurrence. METHOD: A narrative review of significant scientific publications related to the topic and its applicability in endometrial cancer (EC) was performed with the aim of identifying current knowledge about the identification of CSC populations in endometrial cancer, their biological significance, prognostic impact, and therapeutic targeting. RESULTS: Therapy against the tumor population alone has no or negligible effect on CSCs. CSCs, due to their stemness and therapeutic resistance, cause tumor relapse. They target CSCs that may lead to noticeable persistent tumoral regression. Also, they can be used as a predictive marker for poor prognosis. Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that the cultured cells strongly expressed stemness-related genes, such as SOX-2 (sex-determining region Y-box 2), NANOG (Nanog homeobox), and Oct 4 (octamer-binding protein 4). The expression of surface markers CD133+ and CD44+ was found on CSC as stemness markers. Along with surface markers, transcription factors such as NF-kB, HIF-1a, and b-catenin were also considered therapeutic targets. Hypoxia is another vital feature of the tumor environment and aids in the maintenance of the stemness of CSCs. This involves the hypoxic activation of the WNT/b-catenin pathway, which promotes tumor survival and metastasis. Specific antibodies have been investigated against CSC markers; for example, anti-CD44 antibodies have been demonstrated to have potential against different CSCs in preclinical investigations. Anti-CD-133 antibodies have also been developed. Targeting the CSC microenvironment is a possible drug target for CSCs. Focusing on stemness-related genes, such as the transcription pluripotency factors SOX2, NANOG, and OCT4, is another therapeutic option. CONCLUSIONS: Stemness surface and gene markers can be potential prognostic biomarkers and management approaches for cases with drug-resistant endometrial cancers.
未标注：癌症治疗中最大的挑战是肿瘤对传统方法产生耐药性。因此，研究兴趣已转向癌症干细胞群体（CSC）。癌症干细胞是肿瘤内一小部分具有自我更新、分化以及转移/恶性潜能的癌细胞。它们参与肿瘤的起始与发展、转移及复发。 方法：对与该主题及其在子宫内膜癌（EC）中的适用性相关的重要科学出版物进行叙述性综述，目的是确定有关子宫内膜癌中癌症干细胞群体的鉴定、其生物学意义、预后影响及治疗靶向的现有知识。 结果：仅针对肿瘤群体的治疗对癌症干细胞没有或仅有可忽略不计的影响。癌症干细胞由于其干性和治疗耐药性，会导致肿瘤复发。针对癌症干细胞的治疗可能会导致明显的持续性肿瘤消退。此外，它们可用作预后不良的预测标志物。逆转录聚合酶链反应（RT-PCR）表明，培养的细胞强烈表达与干性相关的基因，如SOX-2（性别决定区Y框2）、NANOG（Nanog同源框）和Oct 4（八聚体结合蛋白4）。在癌症干细胞表面发现了表面标志物CD133+和CD44+的表达，作为干性标志物。除了表面标志物外，转录因子如NF-kB、HIF-1a和β-连环蛋白也被视为治疗靶点。缺氧是肿瘤环境的另一个重要特征，有助于维持癌症干细胞的干性。这涉及WNT/β-连环蛋白通路的缺氧激活，从而促进肿瘤存活和转移。已经针对癌症干细胞标志物研究了特异性抗体；例如，在临床前研究中，抗CD44抗体已被证明对不同的癌症干细胞具有潜在作用。抗CD-133抗体也已研发出来。靶向癌症干细胞微环境是针对癌症干细胞的一种可能的药物靶点。关注与干性相关的基因，如转录多能性因子SOX2、NANOG和OCT4，是另一种治疗选择。 结论：干性表面和基因标志物可能是耐药性子宫内膜癌病例的潜在预后生物标志物和管理方法。
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