Evidence mapPaperPMID 42538613Full record

ArticleCancer medicine2026

Predicting Poor Efficacy of Cabozantinib in Advanced Renal Cell Carcinoma by Exploratory Metabolic Pathway Analysis and In Vitro Verification.

Takanari Sakai, Yoshihide Kawasaki, Izumi Sakamoto, Eiji Hishinuma, Naomi Matsukawa, Daigo Chiba, Tomonori Sato, Kento Morozumi, Masamitsu Maekawa, Nariyasu Mano and 1 more

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Article in Cancer medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Takanari SakaiDepartment of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Yoshihide KawasakiDepartment of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.ORCID https://orcid.org/0000-0001-6425-3574
Izumi SakamotoDepartment of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Eiji HishinumaAdvanced Research Center for Innovations in Next-Generation Medicine and Tohoku Medical Megabank Organization, Sendai, Japan.ORCID https://orcid.org/0000-0001-8644-5120
Naomi MatsukawaAdvanced Research Center for Innovations in Next-Generation Medicine and Tohoku Medical Megabank Organization, Sendai, Japan.
Daigo ChibaDepartment of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Tomonori SatoDepartment of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.ORCID https://orcid.org/0000-0001-5659-6809
Kento MorozumiDepartment of Urology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.ORCID https://orcid.org/0000-0002-9651-2371
Masamitsu MaekawaDepartment of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan.ORCID https://orcid.org/0000-0001-6723-0298
Nariyasu ManoDepartment of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan.
Akihiro ItoDepartment of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Funding

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI) 20K07582Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI) 24K12478
6 · The paper itself

Abstract

backgroundCabozantinib (CABO) is currently an essential drug for first-line and sequential therapy in the treatment of advanced renal cell carcinoma (RCC). Predicting its therapeutic efficacy will enable efficient drug selection and improve the prognosis of patients. We conducted an exploratory study to predict the effects of CABO using metabolite analysis with clinical and in vitro samples.

methodsPatients diagnosed with RCC at our hospital between September 2011 and August 2023 who were pathologically diagnosed with clear cell RCC and subsequently received systemic therapy for disease progression or recurrence were included. Patient background, treatment course, and prognosis were retrospectively investigated. Patients were divided into CABO responders and poor responders based on survival analysis. Comprehensive metabolite analysis of serum samples before CABO administration was performed using a non-targeted analysis system (Orbitrap) with a mass spectrometer. The significance of metabolic pathways related to the poor response of CABO analysis was evaluated by establishing CABO-resistant renal cancer cell lines and conducting in vitro quantitative analysis.

resultsA total of 19 analyzable cases were identified during the study period, and seven pathways (methylhistamine metabolism, caffeine metabolism, beta-alanine metabolism, histidine metabolism, glycine and serine metabolism, tryptophan metabolism, and purine metabolism) and five metabolites (methylhistidine, kynurenic acid, xanthine, 7-methylxanthine, and L-2-amino-3-oxobutanoic acid) related to the poor efficacy of CABO were identified in a two-group comparison. Quantitative metabolite analysis of CABO-resistant cell lines established from three different renal cancer cell lines (786-O, ACHN, and Caki-1) confirmed the identified pathways and metabolites in relation to CABO resistance.

conclusionWe identified key metabolites and associated metabolic pathways that may serve as predictive biomarkers for suboptimal cabozantinib efficacy in patients with advanced RCC. While further validation in independent cohorts is warranted, our findings underscore the potential of metabolomic profiling to refine therapeutic selection and improve clinical outcomes.

Indexed as

AnilidesCarcinoma, Renal CellKidney NeoplasmsMetabolic Networks and PathwaysProtein Kinase InhibitorsPyridinesAgedCell Line, TumorDrug Resistance, NeoplasmFemaleHumansMaleMetabolomicsMiddle AgedPrognosisRetrospective StudiesAnilidescabozantinibProtein Kinase InhibitorsPyridinescabozantinibdrug resistanceefficacy predictionmetabolic pathwaysrenal cell carcinoma

Identifiers

PMID42538613
PMCPMC13428040

What Socratic holds

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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.