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靶向癌症治疗中小分子药物设计的最新进展:挑战与未来方向

Recent Advancement in Drug Designing as Small Molecules in Targeted Cancer Therapy: Challenges and Future Directions.

作者信息

Prakash Satya, Tyagi Priyanka, Singh Pratibha, Singh Atul Pratap

机构信息

School of Pharmaceutical Sciences, IIMT University, Meerut, India.

出版信息

Curr Cancer Drug Targets. 2024 Oct 25. doi: 10.2174/0115680096331827240911165227.

Abstract

The adverse outcome that patients experience as a result of anti-cancer therapy failure is primarily caused by metastasis. Making cancer a chronic disease with regular but controlled relapses is the real issue in increasing cancer patient lifespans. This can only be achieved by developing efficient therapeutic techniques that target critical targets in the metastatic process. New targeted therapy medications continue to emerge, and research into the molecular targeted therapy of tumors is flourishing. The ineffectiveness of conventional chemotherapy in targeting metastatic cells is primarily due to its ability to promote the selection of chemo-resistant cell populations that engage in epithelial-to-mesenchymal transition (EMT), which in turn encourages the colonization of distant sites and maintains the initial metastatic process. In considering this circumstance, research into a broad range of small molecules and biologics has been initiated to develop anti-metastatic medications that target particular targets implicated in the different stages of metastasis. With their ability to concentrate on cancer cells while avoiding normal cells, tar-geted medications offer a promising alternative to conventional chemotherapy that is both highly effective and relatively safe. Many obstacles, including an inadequate response rate and drug resistance, persist for small-molecule targeted anti-cancer medications, despite significant ad-vancements in this area. We encouraged small-molecule-focused anti-cancer therapy develop-ment by extensively assessing them by target classification. We reviewed current challenges, listed licenced drugs and key drug candidates in clinical trials for each target, and made sugges-tions for improving anti-cancer drug research and development. This review aims to discuss pre-sent and future small molecule inhibitor research and development for cancer treatment.

摘要

患者因抗癌治疗失败而经历的不良后果主要是由转移引起的。使癌症成为一种有规律但可控制复发的慢性病,是延长癌症患者寿命的真正问题所在。这只能通过开发针对转移过程中关键靶点的有效治疗技术来实现。新的靶向治疗药物不断涌现,肿瘤分子靶向治疗的研究蓬勃发展。传统化疗对转移细胞无效,主要是因为它会促使选择参与上皮-间质转化(EMT)的化疗耐药细胞群体,这反过来又会促进远处部位的定植并维持初始转移过程。考虑到这种情况,已经开始对多种小分子和生物制剂进行研究,以开发针对转移不同阶段所涉及特定靶点的抗转移药物。靶向药物能够集中作用于癌细胞而避免正常细胞,为传统化疗提供了一种有前景的替代方案,既高效又相对安全。尽管小分子靶向抗癌药物在这一领域取得了重大进展,但仍存在许多障碍,包括反应率不足和耐药性。我们通过按靶点分类广泛评估小分子靶向抗癌疗法,鼓励其发展。我们回顾了当前面临的挑战,列出了每个靶点在临床试验中的获批药物和关键候选药物,并对改进抗癌药物研发提出了建议。本综述旨在讨论目前和未来用于癌症治疗的小分子抑制剂的研发情况。

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