| Literature DB >> 32157217 |
Sang-Min Park1, Chae Young Hwang1, Jihye Choi1, Chang Young Joung1, Kwang-Hyun Cho2.
Abstract
Targeted drugs aim to treat cancer by directly inhibiting oncogene activity or oncogenic pathways, but drug resistance frequently emerges. Due to the intricate dynamics of cancer signaling networks, which contain complex feedback regulations, cancer cells can rewire these networks to adapt to and counter the cytotoxic effects of a drug, thereby limiting the efficacy of targeted therapies. To identify a combinatorial drug target that can overcome such a limitation, we developed a Boolean network simulation and analysis framework and applied this approach to a large-scale signaling network of colorectal cancer with integrated genomic information. We discovered Src as a critical combination drug target that can overcome the adaptive resistance to the targeted inhibition of mitogen-activated protein kinase pathway by blocking the essential feedback regulation responsible for resistance. The proposed framework is generic and can be widely used to identify drug targets that can overcome adaptive resistance to targeted therapies.Entities:
Mesh：
Substances：
Year: 2020 PMID： 32157217 DOI： 10.1038/s41388-020-1255-y
Source DB: PubMed Journal: Oncogene ISSN： 0950-9232 Impact factor: 9.867