ArticleNeuro-oncology2022
Multimodal platform for assessing drug distribution and response in clinical trials.
Article in Neuro-oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 13 citations in OpenAlex.
- MALDI-TOF Mass Spectrometry for Glioblastoma Secretome Biomarker Screening: A Review of Challenges and Perspectives.Current issues in molecular biology · 2026Review
- Persistent interferon signaling and clonal expansion mark early events in DNA methylation damage-induced liver cancer.NAR cancer · 2026Article
- From Polyphenols to Prodrugs: Bridging the Blood-Brain Barrier with Nanomedicine and Neurotherapeutics.International journal of molecular sciences · 2026Review
- Characterization and validation of a bone metastatic castration-resistant prostate cancer model as a nanomedicine evaluation platform.Theranostics · 2026Article
- Persistent interferon signaling and clonal expansion mark early events in DNA methylation damage-induced liver cancer.bioRxiv : the preprint server for biology · 2025Article
- Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.Acta neuropathologica communications · 2025Review
- Phase I Study of Adavosertib with Radiotherapy and Temozolomide in Newly Diagnosed Glioblastoma and Intratumoral Drug Levels in Recurrent Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Review
- Cancer 3D Models: Essential Tools for Understanding and Overcoming Drug Resistance.Oncology research · 2025Review
- Decrypting the potency of anti-cancer therapeutics by using mass spectrometry to quantify post-translational modifications.Cell reports methods · 2023Article
- The Blood-Brain Barrier: Implications for Experimental Cancer Therapeutics.Annual review of cancer biology · 2023Article
- Single cell spatial analysis reveals the topology of immunomodulatory purinergic signaling in glioblastoma.Nature communications · 2022Article
- Detection of Label-Free Drugs within Brain Tissue Using Orbitrap Secondary Ion Mass Spectrometry as a Complement to Neuro-Oncological Drug Delivery.Pharmaceutics · 2022Article
Corrections and comments
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Authors and funding
28 authors at 9 institutions in 1 country.
Funding
Abstract
backgroundResponse to targeted therapy varies between patients for largely unknown reasons. Here, we developed and applied an integrative platform using mass spectrometry imaging (MSI), phosphoproteomics, and multiplexed tissue imaging for mapping drug distribution, target engagement, and adaptive response to gain insights into heterogeneous response to therapy.
methodsPatient-derived xenograft (PDX) lines of glioblastoma were treated with adavosertib, a Wee1 inhibitor, and tissue drug distribution was measured with MALDI-MSI. Phosphoproteomics was measured in the same tumors to identify biomarkers of drug target engagement and cellular adaptive response. Multiplexed tissue imaging was performed on sister sections to evaluate spatial co-localization of drug and cellular response. The integrated platform was then applied on clinical specimens from glioblastoma patients enrolled in the phase 1 clinical trial.
resultsPDX tumors exposed to different doses of adavosertib revealed intra- and inter-tumoral heterogeneity of drug distribution and integration of the heterogeneous drug distribution with phosphoproteomics and multiplexed tissue imaging revealed new markers of molecular response to adavosertib. Analysis of paired clinical specimens from patients enrolled in the phase 1 clinical trial informed the translational potential of the identified biomarkers in studying patient's response to adavosertib.
conclusionsThe multimodal platform identified a signature of drug efficacy and patient-specific adaptive responses applicable to preclinical and clinical drug development. The information generated by the approach may inform mechanisms of success and failure in future early phase clinical trials, providing information for optimizing clinical trial design and guiding future application into clinical practice.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.