为了更好的预测大肠癌患者对化疗的反应，科学家利用一种新的数字模型测量不伤害健康组织前提下能够杀死癌症细胞所需应力量。研究结果发表在美国癌症协会制定的《癌症研究》杂志上，研究表明，系统医学法在预测患者化疗反应方面相比其他方法有显著优势。

　　细胞凋亡即程序性细胞死亡，是癌症耐药性的标志。此前的研究表明，细胞凋亡的关键步骤，引起线粒体外膜通透性的进程由BLC-2蛋白质家族的不同成员控制。一些家族成员促进细胞凋亡，一些阻止细胞凋亡。此外，这些蛋白在细胞凋亡方面作用相同并且能够相互替代，这使得预测细胞是否容易凋亡难上加难。

　　为了更好了解大肠癌化疗的决策，研究者开发了一种包含患者特征数据的集合工具。他们研究了BCL-2蛋白，确定特定蛋白质水平并将水平录入数字模型，计算出何种基因毒性应激水平能够实现细胞凋亡。

　　抗结肠癌细胞培养、2期或3期结肠癌患者对于治疗的应答，都是由计算出的细胞凋亡所需的应力水平来精密决定的。研究发现，个别患者BLC-2蛋白质家族水平中异质性程度较高，这是辅助化疗成功与否的关键所在。

　　研究者测试了一种名为“DR/MOMP ”的临床决策工具，并以此确定其在预测结肠癌患者对治疗的反应效果。利用DR/MOMP 能准确预测患者预后。

　　这一发现可能提供一种临床决策的工具，能够预测结肠癌患者的治疗效果。研究提供细胞凋亡的定量动态分析，并能够为个体患者预测治疗效果。

　　New model may help predict response to chemotherapy for colorectal cancer

　　PHILADELPHIA — Scientists may be able to better predict which patients with colorectal cancer will respond to chemotherapy using a new mathematical model that measures the amount of stress required for a cancer cell to die without harming healthy tissue. The results of this study are published in Cancer Research, a journal of the American Association for Cancer Research.

　　"Our study demonstrates that systems medicine approaches (i.e., quantitative analysis of multiple factors in patients' samples combined with mathematical modeling) have a significant advantage over other approaches in predicting therapy responses in patients," said Jochen J.M. Prehn, Ph.D., director of the Centre for Systems Medicine at the Royal College of Surgeons in Ireland.

　　Apoptosis, or programmed cell death, is believed to be a hallmark of cancer resistance to chemotherapy. Prior research has shown that the key step in apoptosis, the process that leads to mitochondrial outer membrane permeabilization (MOMP) is controlled by different members of the BCL-2 family of proteins. Some family members promote apoptosis and some prevent it. In addition, those proteins that have the same effects on apoptosis work in parallel and can substitute for each other, which makes it difficult to predict whether cells are likely or unlikely to die.

　　To better inform decision-making in chemotherapy for colorectal cancer, Prehn and colleagues developed a tool that would incorporate patient-specific, molecular data sets. They studied the BCL-2 proteins, determined levels of the individual proteins and put the levels into a mathematical model that calculated what genotoxic stress level is needed to achieve apoptosis.

　　"Resistance of colon cancer cells in culture, as well as treatment responses of patients with stages 2 and 3 colon cancer, were critically determined by the calculated stress level required to undergo apoptosis," Prehn said. "We found that individual patients had a high degree of heterogeneity in BCL-2 family protein levels and that this was a potential cause of the success or failure of adjuvant chemotherapy."

　　Prehn and colleagues tested a clinical decision-making tool that they call DR_MOMP to determine its use in predicting treatment responses in patients with colon cancer. Using DR_MOMP, they were able to robustly predict patient outcome.

　　"This finding may provide a clinical decision-making tool that enables predictions of treatment responses in patients with colon cancer," Prehn said. "As we provide a quantitative, dynamic analysis of the process of apoptosis, we can also calculate, for individual patients, the therapeutic window."

　　The model could help predict how much genotoxic stress is required for a cancer cell to die before normal tissue is affected. Prehn and colleagues hope to validate DR_MOMP in other cancers and in larger patient cohorts.

　　"We need to develop easy and accessible protein profiling and modeling platforms that enable the implementation of this new technology in clinical trials and in pathology laboratories," Prehn said.