合成致死
PARP抑制剂
癌症研究
DNA修复
医学
癌症
杀伤力
聚ADP核糖聚合酶
生物
DNA
遗传学
内科学
聚合酶
作者
Bac Viet Le,Paulina Podszywałow-Bartnicka,Katarzyna Piwocka,Tomasz Skórski
出处
期刊:Cancers
[MDPI AG]
日期:2022-11-24
卷期号:14 (23): 5795-5795
被引量:5
标识
DOI:10.3390/cancers14235795
摘要
The advanced development of synthetic lethality has opened the doors for specific anti-cancer medications of personalized medicine and efficient therapies against cancers. One of the most popular approaches being investigated is targeting DNA repair pathways as the implementation of the PARP inhibitor (PARPi) into individual or combinational therapeutic schemes. Such treatment has been effectively employed against homologous recombination-defective solid tumors as well as hematopoietic malignancies. However, the resistance to PARPi has been observed in both preclinical research and clinical treatment. Therefore, elucidating the mechanisms responsible for the resistance to PARPi is pivotal for the further success of this intervention. Apart from mechanisms of acquired resistance, the bone marrow microenvironment provides a pre-existing mechanism to induce the inefficiency of PARPi in leukemic cells. Here, we describe the pre-existing and acquired mechanisms of the resistance to PARPi-induced synthetic lethality. We also discuss the potential rationales for developing effective therapies to prevent/repress the PARPi resistance in cancer cells.
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