Antitumor Effects of PRIMA-1 and PRIMA-1(Met) (APR246) in Hematological Malignancies: Still a Mutant P53-Dependent Affair?
Antitumor Effects of PRIMA-1 and PRIMA-1(Met) (APR246) in Hematological Malignancies: Still a Mutant P53-Dependent Affair?
复制标题
DOI：
10.3390/cells10010098
复制
发表时间：
2021-01-07
期刊：
影响因子：
6
通讯作者：
Fronza G
中科院分区：
文献类型：
--
作者：
Menichini P;Monti P;Speciale A;Cutrona G;Matis S;Fais F;Taiana E;Neri A;Bomben R;Gentile M;Gattei V;Ferrarini M;Morabito F;Fronza G
由于其在细胞周期、DNA损伤反应、细胞凋亡、DNA修复、细胞迁移、自噬和细胞代谢中的调节作用，TP53抑癌基因在细胞内稳态中起着关键作用。TP53基因在超过50%的人类癌症中发生突变，尽管其整体功能障碍可能更常见。与实体瘤相比，在血液系统恶性肿瘤中检测到TP53突变的比例较低，但它们的频率通常随着疾病的进展而增加，产生不良反应，如对化疗产生抵抗。由于P53在治疗反应中的关键作用，已经开发了几个分子来重建野生型P53对突变型P53的功能。Prima-1及其甲基化形式Prima-1Met(又称APR246)能够恢复突变型P53的野生型构象并诱导癌细胞凋亡，但它们也具有突变型P53非依赖性特性。本文综述了PRIMA-1和PRIMA-1Met/APR246的活性，并描述了它们在血液系统恶性肿瘤中的潜在应用。
Because of its role in the regulation of the cell cycle, DNA damage response, apoptosis, DNA repair, cell migration, autophagy, and cell metabolism, the TP53 tumor suppressor gene is a key player for cellular homeostasis. TP53 gene is mutated in more than 50% of human cancers, although its overall dysfunction may be even more frequent. TP53 mutations are detected in a lower percentage of hematological malignancies compared to solid tumors, but their frequency generally increases with disease progression, generating adverse effects such as resistance to chemotherapy. Due to the crucial role of P53 in therapy response, several molecules have been developed to re-establish the wild-type P53 function to mutant P53. PRIMA-1 and its methylated form PRIMA-1Met (also named APR246) are capable of restoring the wild-type conformation to mutant P53 and inducing apoptosis in cancer cells; however, they also possess mutant P53-independent properties. This review presents the activities of PRIMA-1 and PRIMA-1Met/APR246 and describes their potential use in hematological malignancies.
登录
查看更多内容
影响因子：
11.4
作者：
Gentile, Massimo;Shanafelt, Tait D.;Morabito, Fortunato
通讯作者：
Morabito, Fortunato
影响因子：
8
作者：
Bykov, VJN;Zache, N;Wiman, KG
通讯作者：
Wiman, KG
影响因子：
51.1
作者：
Al-Sawaf, Othman;Zhang, Can;Fischer, Kirsten
通讯作者：
Fischer, Kirsten
DOI：
10.1073/pnas.88.12.5413
发表时间：
1991-06-01
影响因子：
11.1
作者：
GAIDANO, G;BALLERINI, P;DALLAFAVERA, R
通讯作者：
DALLAFAVERA, R
影响因子：
45.3
作者：
Ahn, Inhye E.;Tian, Xin;Wiestner, Adrian
通讯作者：
Wiestner, Adrian