Chakraborty Rituraj, Dutta Anupam, Mukhopadhyay Rupak
Inflammation and Cancer Biology Laboratory, Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur, Assam, 784028, India.
Clin Transl Oncol. 2025 Jan 11. doi: 10.1007/s12094-024-03841-6.
Globally, breast and ovarian cancers are major health concerns in women and account for significantly high cancer-related mortality rates. Dysregulations and mutations in genes like TP53, BRCA1/2, KRAS and PTEN increase susceptibility towards cancer. Here, we discuss the impact of mutations in the key regulatory gene, TP53 and polymorphisms in its negative regulator MDM2 which are reported to accelerate cancer progression. Missense mutations, null mutations, transversions, transitions, and point mutations occurring in the TP53 gene can cause an increase in metastatic activity. This review discusses mutations occurring in exon regions of TP53, polymorphisms in MDM2 and their interaction with large ribosomal subunit protein (RPL) leading to cancer development. We also highlight the potential of small molecules e.g. p53 activators like XI-011, Tenovin-1, and Nutlin-3a for the treatment of breast and ovarian cancers. The therapeutic efficacy of natural compounds in amelioration of these two types of cancers is also discussed.
在全球范围内，乳腺癌和卵巢癌是女性主要的健康问题，且在癌症相关死亡率中占比极高。TP53、BRCA1/2、KRAS和PTEN等基因的失调和突变会增加患癌易感性。在此，我们讨论关键调控基因TP53的突变及其负调控因子MDM2的多态性所产生的影响，据报道这些会加速癌症进展。TP53基因中发生的错义突变、无效突变、颠换、转换和点突变可导致转移活性增加。本综述讨论了TP53外显子区域发生的突变、MDM2中的多态性及其与大核糖体亚基蛋白（RPL）的相互作用如何导致癌症发展。我们还强调了小分子如XI-011、Tenovin-1和Nutlin-3a等p53激活剂在治疗乳腺癌和卵巢癌方面的潜力。同时也讨论了天然化合物在改善这两种癌症方面的治疗效果。
