Department of Molecular Pharmaceutics, College of Pharmacy, University of Utah, Salt Lake City, UT 84112, USA.
Biomolecules. 2023 Jan 12;13(1):159. doi: 10.3390/biom13010159.
It has been well established that mutations in the tumor suppressor gene, p53, occur readily in a vast majority of cancer tumors, including ovarian cancer. Typically diagnosed in stages three or four, ovarian cancer is the fifth leading cause of death in women, despite accounting for only 2.5% of all female malignancies. The overall 5-year survival rate for ovarian cancer is around 47%; however, this drops to an abysmal 29% for the most common type of ovarian cancer, high-grade serous ovarian carcinoma (HGSOC). HGSOC has upwards of 96% of cases expressing mutations in p53. Therefore, wild-type (WT) p53 and p53-based therapies have been explored as treatment options via a plethora of drug delivery vehicles including nanoparticles, viruses, polymers, and liposomes. However, previous p53 therapeutics have faced many challenges, which have resulted in their limited translational success to date. This review highlights a selection of these historical p53-targeted therapeutics for ovarian cancer, why they failed, and what the future could hold for a new generation of this class of therapies.
已经证实，肿瘤抑制基因 p53 的突变在绝大多数癌症肿瘤中很容易发生，包括卵巢癌。卵巢癌通常在三或四期诊断，尽管仅占所有女性恶性肿瘤的 2.5%，但它却是女性死亡的第五大主要原因。卵巢癌的总体 5 年生存率约为 47%；然而，最常见的卵巢癌类型——高级别浆液性卵巢癌（HGSOC）的生存率却低得惊人，仅为 29%。HGSOC 中有超过 96%的病例表达 p53 突变。因此，野生型（WT）p53 和基于 p53 的治疗方法已通过多种药物递送载体（包括纳米颗粒、病毒、聚合物和脂质体）作为治疗选择进行了探索。然而，以前的 p53 治疗方法面临着许多挑战，这导致它们迄今为止在转化应用方面的成功有限。这篇综述强调了一些针对卵巢癌的历史上的 p53 靶向治疗方法，以及它们失败的原因，以及新一代此类治疗方法的未来前景。
