Impact of KRAS and Co-occurring Mutations on NSCLC Master Regulator Network as Determined by Computational Omics Biology Model.

KRAS is a frequent oncogenic driver in solid tumors, including Non-Small Cell Lung Cancer (NSCLC). KRAS is involved in various signaling pathways that could allow for targeting of KRAS by targeting downstream key transcription factors that mediate oncogene signaling. At the same time, co-occurrence of other mutations alters the signaling pathways and the key transcription factors involved in the disease network. The convergence of these dysregulated pathways to activate key kinases and transcription factors defines master regulators, forming the regulatory logic (i.e. oncotecture) of the tumor cell that maintains the malignant phenotype, its hallmark behaviors, and homeostasis in the face of treatment, while also providing a new set of potential therapeutic targets. In this study, we describe the impact of KRAS and a variety of co-mutations on the tumor’s oncotecture. Journal of Thoracic Oncology 2021 Non-Small Cell Lung Cancer