ArticleNature communications2025
The PIK3CA/AKT pathway drives therapy resistance in rhabdomyosarcoma.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Catalase Defines Radiotherapy Resistance and a Therapeutic Vulnerability in Rhabdomyosarcoma.International journal of molecular sciences · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors.
Funding
Abstract
Olaparib and temozolomide (OT) combination therapy is in clinical trial evaluation for rhabdomyosarcoma (RMS). Unfortunately, OT resistance has been reported in other cancers. Using preclinical mouse xenograft experiments, we show that OT effectively suppresses RMS growth, yet over half of RMS tumors develop resistance associated with transcriptomic changes that occur in the absence of recurrent genomic mutation. Importantly, most resistant RMS models upregulate the PIK3CA/AKT pathway, activating NRF2 phosphorylation and subsequent transcriptional expression of multidrug resistance ABC transporters. PIK3CA inhibitor alpelisib re-sensitizes resistant cells to OT by suppressing expression of ABC transporters. The combination of OT + alpelisib also kills RMS cells which are resistant to standard-of-care combination chemotherapy and was effective in preclinical xenograft mouse models at curbing tumor growth. Our work defines a common resistance pathway in RMS and has credentialled PIK3CA/AKT inhibition as a preclinical strategy to kill therapy resistant RMS.
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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 Socratic graph.