临床前筛查中用于评估抗肿瘤化合物的系统模型、试验和终点参数

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.

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