PARP 抑制剂耐药性的分子机制
Yi Huang1,2, Simin Chen1,2, Nan Yao1,2
1School of Biopharmacy, China Pharmaceutical University, Nanjing 211198, P.R. China.
Oncoscience
|September 25, 2024
概括
聚 (ADP-ribose) 聚合酶 (PARP) 抑制剂 (PARPi) 通过利用HRD缺乏癌症的合成致死性提供向癌症治疗. 本综述探讨了PARPi电阻的机制和克服它的策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 聚 (ADP-ribose) 聚合酶 (PARP) 抑制剂 (PARPi) 代表了癌症治疗的突破,利用合成杀伤性.
- PARPi对具有同源重组修复缺陷 (HRD) 的癌症有效,例如BRCA1/2-突变卵巢,乳腺,胰腺和前列腺癌.
- 四种PARPi (Olaparib,Rucaparib,Niraparib,Talazoparib) 已经获得批准,显著改善了患者的治疗结果.
研究的目的:
- 审查对PARP抑制剂的获得性和新的抗药性背后的分子机制.
- 讨论克服癌症治疗中PARP抑制剂耐药性的新兴策略.
主要方法:
- 关于PARP抑制剂和癌症耐药性的研究的文献综述.
- 对驱动电阻的分子机制的分析.
- 综合当前和未来的治疗策略.
主要成果:
- 通过各种分子变化,可以产生PARPi耐药性,从而降低治疗疗效.
- 了解这些抵抗机制对于开发有效的治疗方法至关重要.
- 目前正在研究几种策略来规避或逆转PARPi电阻.
结论:
- PARPi 耐药性是一个重要的临床挑战,需要进一步研究.
- 开发组合疗法和新的治疗策略对于克服耐药性至关重要.
- 对PARPi耐药机制的持续研究将指导未来的临床应用,并改善癌症患者的生存率.
相关概念视频
02:56Treatment Resistant Cancers
3.3K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.3K
01:02Long-patch Base Excision Repair
7.0K
Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
7.0K
02:37Restarting Stalled Replication Forks
5.8K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.8K
02:37DNA Damage can Stall the Cell Cycle
9.1K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.1K
02:23Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
01:54Base Excision Repair
22.2K
One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
The first step of...
22.2K