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首页> 外文期刊>Journal of experimental & clinical cancer research : >Pharmacology-based ranking of anti-cancer drugs to guide clinical development of cancer immunotherapy combinations
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Pharmacology-based ranking of anti-cancer drugs to guide clinical development of cancer immunotherapy combinations

机译：基于药理学的抗癌药物排名，以指导癌症免疫疗法组合的临床发展

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The success of antibodies targeting Programmed cell death protein 1 (PD-1) and its ligand L1 (PD-L1) in cancer treatment and the need for improving response rates has led to an increased demand for the development of combination therapies with anti-PD-1/PD-L1 blockers as a backbone. As more and more drugs with translational potential are identified, the number of clinical trials evaluating combinations has increased considerably and the demand to prioritize combinations having potential for success over the ones that are unlikely to be successful is rising. This review aims to address the unmet need to prioritize cancer immunotherapy combinations through comprehensive search of potential drugs and ranking them based on their mechanism of action, clinical efficacy and safety. As lung cancer is one of the most frequently studied cancer types, combinations that showed potential for the treatment of lung cancer were prioritized. A literature search was performed to identify drugs with potential in combination with PD-1/PD-L1 blockers and the drugs were ranked based on their mechanism of action and known clinical efficacy. Nineteen drugs or drug classes were identified from an internal list of lead molecules and were scored for their clinical potential. Efficacy and safety data from pivotal studies was summarized for the selected drugs. Further, overlap of mechanisms of action and adverse events was visualized using a heat map illustration to help screen drugs for combinations. The quantitative scoring methodology provided in this review could serve as a template for preliminary ranking of novel combinations.
机译：靶向细胞死亡蛋白1（PD-1）的抗体的成功及其在癌症治疗中的配体L1（PD-L1）和提高响应率的需求导致对抗PD的组合疗法的发展需求增加-1 / PD-L1作为骨干的阻挡仪。随着具有翻译潜力的越来越多的药物，评估组合的临床试验的数量大大增加，要求优先考虑具有不太可能成功的成功潜力的组合的优先考虑的组合。本综述旨在通过全面搜索潜在的药物，并根据其行动机制，临床疗效和安全机制排序，解决未满足的要求优先考虑癌症免疫疗法组合优先考虑癌症免疫疗法组合。由于肺癌是最常见的癌症类型之一，优先考虑了肺癌治疗潜力的组合。进行文献搜索以鉴定具有与PD-1 / PD-L1阻断剂的潜力的药物，并且药物基于其作用机制和已知的临床疗效排序。从铅分子的内部列表中鉴定了19种药物或药物类别，并为其临床潜力进行了评分。枢转研究的功效和安全数据总结了所选药物。此外，使用热图例证可视化动作和不良事件机制的重叠，以帮助筛选组合的药物。本综述中提供的定量评分方法可以作为新颖组合初步排名的模板。

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