KRAS、P53基因突变及MDM2表达与结直肠癌发生的关系

IF 2.3 4区 医学 Q3 ONCOLOGY
Hany A Al-Hussaniy, Amjad I Oraibi, Zahraa Salam Al-Tameemi, Ali Hikmat Alburghaif, Meena Akeel Naji, Fatima Akeel Naji
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引用次数: 0

摘要

背景:结直肠癌(CRC)包括位于直肠乙状结肠交界处、直肠和肛门以及部分结肠的各种癌症。在全球范围内,结直肠癌是癌症相关死亡的第二大原因,也是第三大最常见的恶性肿瘤。KRAS癌基因在30% - 50%的CRC病例中发生突变,导致细胞功能失调。此外,KRAS和P53基因突变与结直肠癌和乳腺癌发病率之间的联系仍然是一个令人感兴趣的领域。方法:从PubMed、谷歌Scholar和ResearchGate等知名数据库中挖掘数据,进行全面的叙述性综述。目的是广泛探索和了解KRAS和P53基因突变与结直肠癌和乳腺癌患病率之间的关系。结果:KRAS癌基因突变已被确定为细胞信号通路的关键参与者,包括MAPK、PI3K和PLD。尽管进行了广泛的研究,但针对这些突变的基因治疗收效甚微,特别是在密码子12、13、61和143中。结论:KRAS和P53基因的突变以及MDM2的异常表达,通过破坏MAPK、PI3K和PLD等关键细胞信号通路,在结直肠癌的发生和发展中起着关键作用。尽管在理解这些机制方面取得了进展,但目前的基因治疗方法已经显示出有限的成功,特别是针对KRAS密码子突变。这强调了迫切需要创新的治疗策略和进一步的研究,以开发有效的治疗结直肠癌及其与其他恶性肿瘤(如乳腺癌)的潜在联系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Association of KRAS and P53 Gene Mutations and MDM2 Expression with the Occurrence of Colorectal Cancer.

Background: Colorectal cancer (CRC) encompasses various cancers located in the rectosigmoid junction, rectum, and anus, as well as parts of the colon. Globally, CRC is the second leading cause of cancer-related mortality and the third most prevalent malignan-cy. The KRAS oncogene was found to be mutated in 30 to 50% of CRC cases, leading to dysregulated cellular functions. Furthermore, the connection between KRAS and P53 gene mutations and the incidence of both colorectal and breast cancer remains an area of interest.

Method: This comprehensive narrative review was carried out by mining data from recog-nized databases, such as PubMed, Google Scholar, and ResearchGate. The purpose was to extensively explore and understand the association between the KRAS and P53 gene muta-tions and the prevalence of colorectal and breast cancers.

Results: The mutation in the KRAS oncogene has been identified as a key player in cellular signaling pathways, including MAPK, PI3K, and PLD. Despite extensive research, gene therapies targeting these mutations have seen limited success, especially in codons 12, 13, 61, and 143.

Conclusion: Mutations in the KRAS and P53 genes, along with aberrant MDM2 expression, play pivotal roles in the onset and progression of colorectal cancer by disrupting key cellular signaling pathways, such as MAPK, PI3K, and PLD. Despite advancements in understand-ing these mechanisms, current gene therapy approaches have shown limited success, particu-larly in targeting KRAS codon mutations. This underscores the urgent need for innovative therapeutic strategies and further research to develop effective treatments for colorectal can-cer and its potential links to other malignancies, such as breast cancer.

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来源期刊
Current cancer drug targets
Current cancer drug targets 医学-肿瘤学
CiteScore
5.40
自引率
0.00%
发文量
105
审稿时长
1 months
期刊介绍: Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.
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