PT  - JOURNAL ARTICLE
AU  - Haswanth Vundavilli
AU  - Aniruddha Datta
AU  - Chao Sima
AU  - Jianping Hua
AU  - Rosana Lopes
AU  - Michael Bittner
TI  - Targeting Oncogenic Mutations in Colorectal Cancer using Cryptotanshinone
AID  - 10.1101/2020.09.15.298398
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.15.298398
4099  - http://biorxiv.org/content/early/2020/09/16/2020.09.15.298398.short
4100  - http://biorxiv.org/content/early/2020/09/16/2020.09.15.298398.full
AB  - 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/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.Competing Interest StatementThe authors have declared no competing interest.