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AI Reveals Cancer Drug Combinations

Organisation news (not new evidence): Biohub's write-up of the Califano-group Nature Genetics study (doi:10.1038/s41588-026-02550-w) on network-based design of combination therapy against coexisting diffuse midline glioma cell states. It states that 8 of 9 drugs depleted the predicted target states in a subcutaneous mouse model, that in orthotopic models depleting one state let non-targeted states dominate, and that avapritinib plus ruxolitinib gave the largest survival gains in mice. Biohub says it is working with partners to build a clinical trial; no trial registration is given.

Authors / organisation: Biohub
Venue: Biohub blog (organisation news)
Date: 2026-08-26
Type: news
Year: 2026
Source: https://biohub.org/blog/cancer-drug-combinations-ai/
Verification: Biohub blog page fetched 2026-10-20 (title, datePublished 2026-08-26, content); underlying study Nature Genetics 2026-04-22 (doi:10.1038/s41588-026-02550-w, abstract via web search); no DMG trial registration found

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Related papers (shared tags)

paperBrain tumor✓ VerifiedVC0183

Systematic design of combination therapy by targeting master regulators of coexisting diffuse midline glioma cell states

Calvo Fernández E, Tomassoni L, Zhang X, Wang J, Obradovic A, Laise P, Griffin AT, Vlahos L, Minns HE, Morales DV, Simmons C, Gallitto M, Wei HJ, Martins TJ, Becker PS, Crawford JR, Tzaridis T, Wechsler-Reya RJ, Garvin J, Gartrell RD, Szalontay L, Zacharoulis S, Wu CC, Zhang Z, Califano A, Pavisic J. · Nature Genetics · 2026-04-22

Calvo Fernández et al. (Califano and Pavisic groups; Nature Genetics 58:1112–1125, 2026) describe a network-based framework to design combination therapies that target complementary coexisting tumor cell states, applied to diffuse midline glioma (DMG). They identify master regulator protein dependencies in seven coexisting cell states (confirmed by pooled CRISPR–Cas9 assays) and use perturbational transcriptional profiles of 372 clinically relevant drugs to prioritize candidates predicted to invert state-specific master regulator activity. State-selective drug sensitivity was validated in vivo for 8 of 9 drugs (including avapritinib, ruxolitinib and larotrectinib); in these preclinical experiments, avapritinib plus ruxolitinib extended median survival nearly threefold versus vehicle and 1.5-fold versus avapritinib alone. No clinical data are reported. Declared interests: A.C. is a founder and equity holder of DarwinHealth, which licenses some of the algorithms used.

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Tahoe Therapeutics, Arc Institute, and Biohub Partner to Generate the Largest Perturbation Dataset for Virtual Cell Models

Tahoe Therapeutics; Arc Institute; Biohub · Tahoe news (company announcement) · 2026-01-12

Company announcement, not independent evidence; older item added as a gap fill: Tahoe Therapeutics, Arc Institute and Biohub announce a jointly curated dataset for which Tahoe will generate more than 120 million single-cell data points across 225,000 drug–patient interactions with its Mosaic platform, described as more than 4x as perturbation-rich as Tahoe-100M; data are to be shared among the three first and ultimately released open source (no release date given).

Source

paperBrain tumor✓ VerifiedVC0172

Neoplastic and non-neoplastic astrocyte states converge on mesenchymal and injury-response programs during glioblastoma recurrence

Lindgren D, Rosberg R, Smolag KI, Johansson E, Braun S, Sjölund J, Manou D, Pracucci E, Phung B, Harbst K, Jeannot P, So YC, Bolivar P, Malmberg M, Ceberg C, Bengzon J, Ahlenius H, Jönsson GB, Pietras K, Pietras A. · Cell Reports · 2026-10-15

Lindgren et al. (Lund University; Cell Reports 2026) profile healthy brain, primary tumors and post-radiotherapy recurrences in a genetically engineered glioblastoma mouse model with single-cell and spatial transcriptomics and immunofluorescence, across 13 non-neoplastic cell types and 10 tumor cell states. They report reactive non-neoplastic astrocytes and tumor cells adopting reactive astrocyte-like phenotypes; reactive astrocyte-like tumor cells with mesenchymal and injury-response signatures are enriched after radiotherapy and persist in recurrences. The authors propose these convergent programs as potential mediators of radioresistance (mouse model; not tested in patients).

DOI PubMed

paperBrain tumor✓ VerifiedVC0078