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基因治疗靶向 p53 和 KRAS 治疗结直肠癌:是神话还是未来之路?

Gene Therapy Targeting p53 and KRAS for Colorectal Cancer Treatment: A Myth or the Way Forward?

机构信息

Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia.

出版信息

Int J Mol Sci. 2021 Nov 3;22(21):11941. doi: 10.3390/ijms222111941.

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy worldwide and is responsible as one of the main causes of mortality in both men and women. Despite massive efforts to raise public awareness on early screening and significant advancements in the treatment for CRC, the majority of cases are still being diagnosed at the advanced stage. This contributes to low survivability due to this cancer. CRC patients present various genetic changes and epigenetic modifications. The most common genetic alterations associated with CRC are p53 and KRAS mutations. Gene therapy targeting defect genes such as (tumor suppressor gene encodes for p53) and (oncogene) in CRC potentially serves as an alternative treatment avenue for the disease in addition to the standard therapy. For the last decade, significant developments have been seen in gene therapy for translational purposes in treating various cancers. This includes the development of vectors as delivery vehicles. Despite the optimism revolving around targeted gene therapy for cancer treatment, it also has various limitations, such as a lack of availability of related technology, high cost of the involved procedures, and ethical issues. This article will provide a review on the potentials and challenges of gene therapy targeting p53 and KRAS for the treatment of CRC.

摘要

结直肠癌(CRC)是全球第三大常见恶性肿瘤,也是男性和女性主要死亡原因之一。尽管为提高公众对早期筛查的认识做出了巨大努力,并在 CRC 的治疗方面取得了重大进展,但大多数病例仍在晚期诊断。这导致了这种癌症的存活率低。CRC 患者表现出各种遗传变化和表观遗传修饰。与 CRC 相关的最常见遗传改变是 p53 和 KRAS 突变。针对缺陷基因的基因治疗,如(肿瘤抑制基因编码 p53)和(癌基因),除了标准治疗外,可能为该疾病提供一种替代治疗途径。在过去的十年中,基因治疗在治疗各种癌症的转化方面取得了重大进展。这包括作为载体的开发。尽管针对癌症治疗的靶向基因治疗前景乐观,但它也存在各种限制,例如相关技术的缺乏、所涉及程序的高成本和伦理问题。本文将综述针对 p53 和 KRAS 的基因治疗在治疗 CRC 方面的潜力和挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb19/8584926/500799dde54d/ijms-22-11941-g001.jpg

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