Gasparri Maria Luisa, Bardhi Erlisa, Ruscito Ilary, Papadia Andrea, Farooqi Ammad Ahmad, Marchetti Claudia, Bogani Giorgio, Ceccacci Irene, Mueller Michael D, Benedetti Panici Pierluigi
Department of Gynecology, Obstetrics and Urology, "Sapienza" University of Rome, Rome, Italy.
Department of Obstetrics and Gynecology, University of Berne, Berne, Switzerland.
Geburtshilfe Frauenheilkd. 2017 Oct;77(10):1095-1103. doi: 10.1055/s-0043-118907. Epub 2017 Oct 26.
The high recurrence rate and the low overall survival in ovarian cancer suggest that a more specific therapeutic approach in addition to conventional treatment is required. Translational and clinical research is investigating new molecular targets in order to find an alternative way to affect tumor growth and to minimize the overlap of toxicity of antiblastic agents. Given its implication in many cellular activities including regulation of cell growth, motility, survival, proliferation, protein synthesis, autophagy, transcription, as well as angiogenesis, PI3K/AKT/mTOR is one of the most investigated intracellular signaling pathways. A dis-regulation of this pathway has been shown in several tumors, including ovarian cancer. In this setting, mTor proteins represent a potential target for inhibitors, which could ultimately play a pivotal role in counteracting cellular proliferation. Recently, mTor inhibitors have been approved in the treatment of pancreatic neuroendocrine tumors, mantle cell lymphoma and renal cancer. Clinical trials have assessed the safety of these drugs in ovarian cancer patients. Ongoing phase I and II studies are evaluating the oncologic outcome of mTor inhibitor treatment and its effect in combination with conventional chemotherapy and target agents.
卵巢癌的高复发率和低总生存率表明，除了传统治疗方法外，还需要一种更具特异性的治疗方法。转化医学和临床研究正在探索新的分子靶点，以寻找影响肿瘤生长的替代方法，并尽量减少抗瘤药物毒性的重叠。鉴于PI3K/AKT/mTOR参与许多细胞活动，包括细胞生长、运动、存活、增殖、蛋白质合成、自噬、转录以及血管生成的调节，它是研究最多的细胞内信号通路之一。该信号通路的失调已在包括卵巢癌在内的多种肿瘤中得到证实。在这种情况下，mTor蛋白是抑制剂的潜在靶点，抑制剂最终可能在对抗细胞增殖中发挥关键作用。最近，mTor抑制剂已被批准用于治疗胰腺神经内分泌肿瘤、套细胞淋巴瘤和肾癌。临床试验评估了这些药物在卵巢癌患者中的安全性。正在进行的I期和II期研究正在评估mTor抑制剂治疗的肿瘤学结果及其与传统化疗和靶向药物联合使用的效果。
