Patient-specific Boolean models of signalling networks guide personalised treatments

• DOI: 10.7554/elife.72626
• Publication Date: 2022-02-15T00:01:16Z
• Authors: Arnau Montagud; Jonas Béal; Luis Tobalina; Pauline Traynard; Vigneshwari Subra...; Bence Szalai; Róbert Alföldi; László Puskás; Alfonso Valencia; Emmanuel Barillot; Julio Saez-Rodriguez; Laurence Calzone
• Keywords: Signalling

Prostate cancer is the second most occurring in men worldwide. To better understand mechanisms of tumorigenesis and possible treatment responses, we developed a mathematical model prostate which considers major signalling pathways known to be deregulated. We personalised this Boolean molecular data reflect heterogeneity specific response perturbations patients. A total 488 samples were used build patient-specific models compared available clinical data. Additionally, eight cell line-specific built validate our approach with dose-response several drugs. The effects single combined drugs tested these under different growth conditions. identified 15 actionable points interventions one whose inactivation hinders tumorigenesis. results, nine small molecule inhibitors five those putative targets found dose-dependent effect on four them, notably targeting HSP90 PI3K. These results highlight predictive power illustrate how they can for precision oncology.