Department of Electrical and Computer Engineering, Texas A&M University, College Station, Texas, United States of America.
TEES-AgriLife Center for Bioinformatics and Genomic Systems Engineering (CBGSE), College Station, Texas, United States of America.
PLoS One. 2021 Feb 17;16(2):e0247190. doi: 10.1371/journal.pone.0247190. eCollection 2021.
Colorectal cancer (CRC) is one of the most prevalent types of cancer in the world and ranks second in cancer deaths in the US. Despite the recent improvements in screening and treatment, the number of deaths associated with CRC is still very significant. The complexities involved in CRC therapy stem from multiple oncogenic mutations and crosstalk between abnormal pathways. This calls for using advanced molecular genetics to understand the underlying pathway interactions responsible for this cancer. In this paper, we construct the CRC pathway from the literature and using an existing public dataset on healthy vs tumor colon cells, we identify the genes and pathways that are mutated and are possibly responsible for the disease progression. We then introduce drugs in the CRC pathway, and using a boolean modeling technique, we deduce the drug combinations that produce maximum cell death. Our theoretical simulations demonstrate the effectiveness of Cryptotanshinone, a traditional Chinese herb derivative, achieved by targeting critical oncogenic mutations and enhancing cell death. Finally, we validate our theoretical results using wet lab experiments on HT29 and HCT116 human colorectal carcinoma cell lines.
结直肠癌（CRC）是世界上最常见的癌症类型之一，也是美国癌症死亡人数排名第二的癌症。尽管最近在筛查和治疗方面有所改进，但与 CRC 相关的死亡人数仍然非常显著。CRC 治疗的复杂性源于多种致癌突变和异常途径之间的相互作用。这就需要利用先进的分子遗传学来了解导致这种癌症的潜在途径相互作用。在本文中，我们从文献中构建了 CRC 途径，并使用现有的关于健康与肿瘤结肠细胞的公共数据集，确定了发生突变并可能导致疾病进展的基因和途径。然后，我们在 CRC 途径中引入药物，并使用布尔建模技术，推导出产生最大细胞死亡的药物组合。我们的理论模拟表明，通过靶向关键致癌突变和增强细胞死亡，一种传统中药丹参酮衍生物 Cryptotanshinone 可以达到治疗效果。最后，我们使用 HT29 和 HCT116 人结直肠癌细胞系的湿实验室实验验证了我们的理论结果。
