Liu Bin, Wang Ziyu, Gu Meng, Wang Jinghui, Tan Jinjing
Cancer Research Center, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
Transl Lung Cancer Res. 2024 Aug 31;13(8):2067-2081. doi: 10.21037/tlcr-24-592. Epub 2024 Aug 28.
Lung cancer remains a leading cause of cancer-related mortality globally, with drug resistance posing a significant challenge to effective treatment. The advent of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (CRISPR-Cas9) technology offers a novel and precise gene-editing technology for targeting and negating drug resistance mechanisms in lung cancer. This review summarizes the research progress in the use of CRISPR-Cas9 technology for investigating and managing drug resistance in lung cancer treatment.
A literature search was conducted using the Web of Science and PubMed databases, with the following keywords: [CRISPR-Cas9], [lung cancer], [drug resistance], [gene editing], and [gene therapy]. The search was limited to articles published in English from 2002 to September 2023. From the search results, studies that utilized CRISPR-Cas9 technology in the context of lung cancer drug resistance were selected for further analysis and summarize.
CRISPR-Cas9 technology enables precise DNA-sequence editing, allowing for the targeted addition, deletion, or modification of genes. It has been applied to investigate drug resistance in lung cancer by focusing on key genes such as epidermal growth factor receptor (), Kirsten rat sarcoma viral oncogene homolog (), tumor protein 53 (), and B-cell lymphoma/leukemia-2 (), among others. The technology has shown potential in inhibiting tumor growth, repairing mutations, and enhancing the sensitivity of cancer cells to chemotherapy. Additionally, CRISPR-Cas9 has been used to identify novel key genes and molecular mechanisms contributing to drug resistance, offering new avenues for therapeutic intervention. The review also highlights the use of CRISPR-Cas9 in targeting immune escape mechanisms and the development of strategies to improve drug sensitivity.
The CRISPR-Cas9 technology holds great promise for advancing lung cancer treatment, particularly in addressing drug resistance. The ability to precisely target and edit genes involved in resistance pathways offers a powerful tool for developing more effective and personalized therapies. While challenges remain in terms of delivery, safety, and ethical considerations, ongoing research and technological refinements are expected to further enhance the role of CRISPR-Cas9 in improving patient outcomes in lung cancer treatment.
肺癌仍然是全球癌症相关死亡的主要原因，耐药性对有效治疗构成了重大挑战。成簇规律间隔短回文重复序列（CRISPR）和CRISPR相关蛋白9（CRISPR-Cas9）技术的出现，为靶向和消除肺癌耐药机制提供了一种新颖且精确的基因编辑技术。本综述总结了利用CRISPR-Cas9技术在肺癌治疗中研究和管理耐药性的研究进展。
使用Web of Science和PubMed数据库进行文献检索，关键词如下：[CRISPR-Cas9]、[肺癌]、[耐药性]、[基因编辑]和[基因治疗]。检索限于2002年至2023年9月发表的英文文章。从检索结果中，选择在肺癌耐药背景下利用CRISPR-Cas9技术的研究进行进一步分析和总结。
CRISPR-Cas9技术能够实现精确的DNA序列编辑，允许对基因进行靶向添加、删除或修饰。它已被应用于通过关注关键基因，如表皮生长因子受体（）、 Kirsten大鼠肉瘤病毒癌基因同源物（）、肿瘤蛋白53（）和B细胞淋巴瘤/白血病-2（）等来研究肺癌的耐药性。该技术在抑制肿瘤生长、修复突变以及增强癌细胞对化疗的敏感性方面显示出潜力。此外，CRISPR-Cas9已被用于识别导致耐药性的新关键基因和分子机制，为治疗干预提供了新途径。本综述还强调了CRISPR-Cas9在靶向免疫逃逸机制以及开发提高药物敏感性策略方面的应用。
CRISPR-Cas9技术在推进肺癌治疗，特别是解决耐药性方面具有巨大潜力。精确靶向和编辑耐药途径中涉及基因的能力，为开发更有效和个性化的疗法提供了有力工具。虽然在递送、安全性和伦理考量方面仍存在挑战，但持续的研究和技术改进有望进一步增强CRISPR-Cas9在改善肺癌治疗患者预后方面的作用。
