摘要
药物组合的临床前评价是具有挑战性的。这篇小综述里,我们讨论合成致死性的概念,以及如何可能会影响药物组合和临床开发的评价。我们也将审查新的药物组合与免疫制剂和伴随的致死性的概念。我们建议,合成致死性的相互作用的识别,包括使用新的药物组合伴随的致命性,可以加速药物开发过程。这种方法可能识别肿瘤与特定的分子改变的协同组合,限制了对正常组织的毒性。此外癌细胞的靶向药物与免疫治疗的结合有可能作用于不同的功能,没有重叠的毒性。这里,我们还讨论了这种方法可能在早期临床研究设计的结果。
关键词: 合成致死性,药物组合,治疗指数,免疫制剂,免疫治疗,癌症。
Current Cancer Drug Targets
Title:Novel Synthetic Lethality Approaches for Drug Combinations and Early Drug Development
Volume: 17 Issue: 1
Author(s): Alberto Ocana and Atanasio Pandiella
Affiliation:
关键词: 合成致死性,药物组合,治疗指数,免疫制剂,免疫治疗,癌症。
摘要: Preclinical evaluation of drug combinations is challenging. In this mini-review we discuss the concept of synthetic lethality and how this can impact on the evaluation of drug combinations and its clinical development. We will also review novel combinations with immunologic agents and the concept of collateral lethality. We suggest that identification of synthetic lethality interactions including collateral lethality using novel drug combinations can speed up the drug development process. This approach may identify synergistic combinations in tumors with a specific molecular alteration, limiting toxicity to normal tissue. In addition, the combination of an immunotherapy with an agent targeting cancer cells have the potential for acting on different functions with no overlapping of toxicities. Here, we also discuss potential consequences of this approach in the design of early clinical studies.
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Cite this article as:
Alberto Ocana and Atanasio Pandiella , Novel Synthetic Lethality Approaches for Drug Combinations and Early Drug Development, Current Cancer Drug Targets 2017; 17 (1) . https://dx.doi.org/10.2174/1568009616666151203224714
DOI https://dx.doi.org/10.2174/1568009616666151203224714 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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