Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cell Chem Biol. 2023 Sep 21;30(9):1156-1168.e7. doi: 10.1016/j.chembiol.2023.08.007. Epub 2023 Sep 8.
A challenge for screening new anticancer drugs is that efficacy in cell culture models is not always predictive of efficacy in patients. One limitation of standard cell culture is a reliance on non-physiological nutrient levels, which can influence cell metabolism and drug sensitivity. A general assessment of how physiological nutrients affect cancer cell response to small molecule therapies is lacking. To address this, we developed a serum-derived culture medium that supports the proliferation of diverse cancer cell lines and is amenable to high-throughput screening. We screened several small molecule libraries and found that compounds targeting metabolic enzymes were differentially effective in standard compared to serum-derived medium. We exploited the differences in nutrient levels between each medium to understand why medium conditions affected the response of cells to some compounds, illustrating how this approach can be used to screen potential therapeutics and understand how their efficacy is modified by available nutrients.
筛选新的抗癌药物面临的一个挑战是，细胞培养模型中的疗效并不总是能预测患者的疗效。标准细胞培养的一个局限性是依赖于非生理的营养水平，这会影响细胞代谢和药物敏感性。缺乏对生理营养如何影响癌细胞对小分子治疗反应的全面评估。为了解决这个问题，我们开发了一种血清衍生的培养基，它支持多种癌细胞系的增殖，并且适合高通量筛选。我们筛选了几种小分子文库，发现针对代谢酶的化合物在标准培养基和血清衍生培养基中的效果有差异。我们利用两种培养基中营养水平的差异来了解为什么培养基条件会影响细胞对某些化合物的反应，说明了这种方法如何用于筛选潜在的治疗药物，并了解其疗效如何被可用的营养物质所修饰。
