Jonathan R. Dry

Nov 11, 2024 | cell.com | Rei Kudo |Anton Safonov |Catherine Jones |Jonathan R. Dry

Main text(Cancer Cell , 1919–1935.e9; November 11, 2024)We, the authors of this paper, recently reported that loss of in hormone receptor-positive breast cancer associated with long-term failure to CDK4/6 inhibitors due to geroconversion. Upon online publication of the article, we realized that we had inadvertently omitted Iker Huerga Sanchez (I.H.S.) from the author list.

Oct 10, 2024 | cell.com | Rei Kudo |Anton Safonov |Catherine Jones |Jonathan R. Dry

SA- β-gal assaysCells were treated with DMSO, 50 nM abemaciclib or 500 nM evbaciclib for 5–8 days. Cells were harvested using trypsin/EDTA and then stained with the CellEvent Senescence Green Flow Cytometry Assay Kit (Invitrogen, C10840) according to the manufacturer’s instructions. Briefly, cells were fixed with 2% paraformaldehyde for 15 min at room temperature and stained with the CellEvent Senescence Green Probe for 2 h at 37°C without CO2.

Jun 21, 2024 | nature.com | Sebestyén Kamp |Balint Farkas |Jonathan R. Dry |Duncan Young |Ben Sidders |Krishna C. Bulusu | +9 more

Combination therapy is well established as a key intervention strategy for cancer treatment, with the potential to overcome monotherapy resistance and deliver a more durable efficacy. However, given the scale of unexplored potential target space and the resulting combinatorial explosion, identifying efficacious drug combinations is a critical unmet need that is still evolving. In this paper, we demonstrate a network biology-driven, simulation-based solution, the Simulated Cell™. Integration of omics data with a curated signaling network enables the accurate and interpretable prediction of 66,348 combination-cell line pairs obtained from a large-scale combinatorial drug sensitivity screen of 684 combinations across 97 cancer cell lines (BAC = 0.62, AUC = 0.7). We highlight drug combination pairs that interact with DNA Damage Response pathways and are predicted to be synergistic, and deep network insight to identify biomarkers driving combination synergy. We demonstrate that the cancer cell ‘avatars’ capture the biological complexity of their in vitro counterparts, enabling the identification of pathway-level mechanisms of combination benefit to guide clinical translatability.