摘要
抗肿瘤治疗方法的有效性取决于这些药物选择性的消除恶性细胞,且对正常的细胞几乎没有毒性。在人类大部分肿瘤中一个非常罕见的与化疗相关的肿瘤干细胞(CSCs)的出现,导致了“干细胞理论(SCT)”。SCT提出的观点是消除这一部分将导致癌症的最终治愈,但是实验数据显示这个经典的观点是有争议的,并且目前正逐步被其他模型所替代。这些新型的癌症生物模型预测到在治愈癌症中,只使用药物或者联合药物治疗并一次消除所有的(CSCs 和非-CSCs),称之为“pankiller药物”,将是有效。对于“pankiller药物”需要的测试评估有(i)体外系统中所有癌症细胞的清除(ii)体内系统中根除肿瘤和预防肿瘤复发的能力。但是,在目前,大部分实验中被测试的药物只能够提供抗肿瘤化合物短期效果的境况。这也部分解释了为什么只有一小部分的药物能够进入到临床试验中并被实际批准用于临床使用。这篇文章将以筛选潜在抗肿瘤药物为目的的常规使用的系统,试验和终端参数的提供一个精简的综述,基于当前对癌症生物学的知识,提出一个更加合理的抗肿瘤药物筛选方案。
关键词: 系统模型,试验,终端参数,抗肿瘤,药物筛选,临床前。
Current Medicinal Chemistry
Title:System Models, Assays and Endpoint Parameters to Evaluate Anticancer Compounds During Preclinical Screening
Volume: 21 Issue: 35
Author(s): Juan Sebastian Yakisich
Affiliation:
关键词: 系统模型,试验,终端参数,抗肿瘤,药物筛选,临床前。
摘要: The effectiveness of anticancer therapies relies on the ability of these substances to selectively eliminate the malignant cells with little or no toxicity to normal cells. The isolation in most human tumors of a rare subpopulation of cancer stem cells (CSCs) associated with chemo resistance leads to the “stem cell theory” (SCT). The SCT proposed that eliminating this fraction will eventually cure cancer but experimental data supporting this classical view are controversial and now being gradually replaced by other models. These novel models of cancer biology predict that to cure cancer only drugs or combination of drugs that eliminate all (CSCs and non-CSCs) cancer cells at once (“pankiller drugs”) will be effective. The search for “pankiller drugs” will require tests to assess (i) the elimination of all cancer cells in in vitro systems (ii) the ability to eradicate the tumors and prevent tumor relapse in in vivo systems. However, at present, most drugs are being tested in assays that can only provide a picture of the short term activity of anticancer compounds. This in part explains why only a small fraction of the drugs that enter clinical trials are actually approved for clinical use. This article will provide a concise review of the systems, assays and endpoint parameters routinely used to screen for potential anticancer drugs and propose, based in the current knowledge of cancer biology, a more rationale anticancer drug screening program.
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Cite this article as:
Yakisich Sebastian Juan, System Models, Assays and Endpoint Parameters to Evaluate Anticancer Compounds During Preclinical Screening, Current Medicinal Chemistry 2014; 21 (35) . https://dx.doi.org/10.2174/09298673113209990009
DOI https://dx.doi.org/10.2174/09298673113209990009 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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