ReviewReported positivePreclinical onlyTier 1 · lab
Molecular biology reports · May 2026 · narrative review
Genisteinbreast cancerovarian cancerprostate cancergliomaneuroblastomahepatocellular carcinomalung cancerbladder cancerosteosarcomarhabdomyosarcoma This is a narrative review of the biological activities and potential therapeutic roles of soy isoflavones (including genistein and daidzein). The authors summarize proposed anticancer mechanisms (estrogen receptor modulation, apoptosis, anti-angiogenesis, epigenetic effects, etc.) and report that in vitro and in vivo studies have shown promising results across a range of tumor types. They conclude that further research—especially studies combining isoflavones with established chemotherapeutics—is needed.
Studied with: chemotherapeutic agents.
Key findings
- Soy isoflavones (genistein, daidzein) have estrogenic and non-estrogenic activities including anti-inflammatory, antioxidant, and immunomodulatory effects.
- Proposed anticancer mechanisms include modulation of estrogen receptors, copper ion-dependent induction of cell death, promotion of apoptosis, inhibition of angiogenesis and metastasis, regulation of epigenetic processes, and effects on platelet function.
- Because of estrogen receptor interactions, isoflavones have been studied particularly in hormone-dependent cancers such as breast, ovarian, and prostate cancer.
- In vitro and in vivo studies have reported promising results in multiple malignancies (gliomas, neuroblastoma, hepatocellular carcinoma, lung and bladder cancers, osteosarcoma, rhabdomyosarcoma).
- Authors recommend further investigation, particularly combining isoflavones with established chemotherapeutics, to evaluate potential synergy.
Limitations: This article is a narrative review and does not present new clinical trial data.; The evidence summarized is primarily preclinical (in vitro and in vivo) with no clinical trial data provided in the abstract.; Mechanistic proposals are not proven clinical effects and require further experimental and clinical validation.; Safety and efficacy in patients, optimal dosing, and interactions with standard therapies are not established in this review..
AI summary of the abstract, human-reviewed · Jul 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human · observationalMechanismMixed resultsLimited evidenceTier 3 · early humann = 42
Neuro-oncology · Sep 2025 · retrospective case series (screening institutional datasets and published institutional cases)
central nervous system neuroblastomahigh-grade gliomadiffuse midline glioma (H3 K27M-mutant)radiation-associated tumorembryonal tumorpineoblastoma
Researchers analyzed 42 human CNS tumors with FOXR2 overexpression from institutional datasets and published cases to describe their histologic, molecular, imaging, and clinical features. FOXR2 activation was found across multiple CNS tumor types (including high-grade gliomas, diffuse midline gliomas, embryonal tumors, and pineoblastomas) and arose by mechanisms such as promoter donation, enhancer hijacking, alternative promoter usage, and truncated LINE-1 retrotransposition. Downstream epigenomic and transcriptomic effects were shared across tumor types, but clinical outcomes differed: FOXR2-positive DMGs and pineoblastomas had very poor 2-year survival, while CNS neuroblastomas showed favorable responses to combined chemotherapy and radiation.
Reported effects: n_total_tumors 42, n=42 · HGG_count 21, n=21 · +9 more
Key findings
- 42 CNS tumors with FOXR2 overexpression were analyzed.
- Tumor composition: 21 (50.0%) were high-grade gliomas (HGGs) and 18 (42.9%) were embryonal tumors.
- HGG subgroup included ten H3 K27M-mutant diffuse midline gliomas and eight radiation-associated tumors.
- Embryonal subgroup included 11 CNS neuroblastomas and six pineoblastomas.
- FOXR2 expression was similar between CNS neuroblastoma and other tumor types (P = 0.82).
- Most FOXR2 activation mechanisms involved structural alterations causing promoter donation and enhancer hijacking from active genes essential for brain development; other mechanisms included alternative promoter activation and truncated LINE-1 retrotransposition.
- All but two aberrant FOXR2 transcripts incorporated non-canonical, non-coding exons.
- Gene set enrichment analysis showed shared downstream epigenomic and transcriptomic effects of FOXR2 activation across tumor types.
- Clinical outcomes varied by tumor type: DMGs and pineoblastomas with FOXR2 overexpression had 0% 2-year overall survival, whereas CNS neuroblastomas 'responded well' to combined chemotherapy and radiation.
Limitations: Retrospective case series assembled from institutional datasets and published cases, with potential selection bias.; Small overall sample size (n=42) and small subgroup sizes limit statistical power.; Heterogeneous cohort (multiple tumor histologies and prior radiation–associated tumors) limits generalizability.; Observational molecular analysis without reported prospective validation or functional in vivo confirmation of mechanisms.; Clinical outcome comparisons are descriptive and may be confounded by differing treatments and patient characteristics..
AI summary of the abstract, human-reviewed · Sep 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Animal studyReported positivePreclinical onlyTier 2 · animal
Nature communications · Aug 2025 · xenograft antitumor assays
neuroblastomarhabdomyosarcomacolorectal carcinomamelanomaovarian carcinomabreast carcinoma
This study tested a humanized antibody-drug conjugate called CDX0239-PBD in ALK-expressing cancer models. In cell lines, it was taken up by ALK-positive neuroblastoma cells and killed them in a way that depended on surface ALK expression. In mouse xenograft models, it produced strong antitumor activity and complete responses were maintained in several ALK-expressing cancers.
Key findings
- ALK RNA, protein, and tumor cell surface expression was elevated in multiple pediatric and adult malignancies with minimal expression in childhood normal tissues.
- CDX0239-PBD was internalized in ALK-expressing neuroblastoma cell lines with cell surface expression-dependent cytotoxicity.
- CDX0239-PBD exhibited potent antitumor efficacy including maintained complete responses in ALK-expressing patient and cell line-derived neuroblastoma, fusion-positive rhabdomyosarcoma, and colorectal carcinoma xenograft models.
Limitations: Preclinical study only; no human treatment data are reported in the abstract.; Efficacy was shown in cell lines and xenograft mouse models, which may not predict clinical benefit.; No quantitative effect sizes, dosing details, or toxicity results are provided in the abstract..
The abstract describes a preclinical anticancer antibody-drug conjugate targeting ALK-expressing tumors.
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text