Patient-specific logic models of signaling pathways from screenings on cancer biopsies to prioritize personalized combination therapies.

ABSTRACT: Mechanistic modeling of signaling pathways mediating patient-specific response to therapy can help to unveil resistance mechanisms and improve therapeutic strategies. Yet, creating such models for patients, in particular for solid malignancies, is challenging. A major hurdle to build these models is the limited material available that precludes the generation of large-scale perturbation data. Here, we present an approach that couples ex vivo high-throughput screenings of cancer biopsies using microfluidics with logic-based modeling to generate patient-specific dynamic models of extrinsic and intrinsic apoptosis signaling pathways. We used the resulting models to investigate heterogeneity in pancreatic cancer patients, showing dissimilarities especially in the PI3K-Akt pathway. Variation in

SUBMITTER: Eduati F 

PROVIDER: S-EPMC7029724 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature