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 · observationalMechanismReported positiveLimited evidenceTier 3 · early humann = 31
Histopathology · Apr 2026 · molecular DNA methylation and copy-number profiling of a series of uterine tumours
GREB1-rearranged uterine tumourUTROSCT (uterine tumour resembling ovarian sex cord tumour)uterine smooth muscle tumours (leiomyoma, leiomyosarcoma)endometrial stromal sarcomaembryonal rhabdomyosarcomaSMARCA4-deficient uterine sarcoma
The authors performed global DNA methylation and copy-number analyses on 10 GREB1-rearranged uterine tumours and 21 classic UTROSCTs (including 7 with ESR1::NCOA2/3 fusions). GREB1-rearranged tumours shared a DNA methylation cluster with UTROSCTs and were distinct from other uterine sarcoma types, but showed greater genomic complexity (more copy-number alterations) and more often lacked overt sex cord morphology.
Reported effects: Number of GREB1-rearranged uterine tumours 10 · Number of classic UTROSCTs 21 · +2 more
Key findings
- GREB1-rearranged uterine tumours show overlap in global methylation profiles with UTROSCT, including ESR1::NCOA2/3 positive cases, forming a DNA methylation cluster separate from several other uterine sarcoma types.
- GREB1-rearranged tumours displayed a greater degree of genomic complexity with more extensive copy number alterations than conventional UTROSCTs, including those with ESR1::NCOA2/3.
- GREB1-rearranged tumours frequently lacked overt sex cord morphology: only 1 GREB1-rearranged tumour displayed a prominent trabecular pattern while the remaining cases had diffuse/solid growth.
- All 7 ESR1::NCOA2/3-positive UTROSCTs demonstrated corded, nested, trabecular and/or tubular/sertoliform patterns.
Limitations: Small case series (31 tumours total) limits generalisability.; Observational molecular profiling without clinical outcome or functional validation data.; Comparisons are limited to the tumour types included; methylation/copy-number differences may not generalise to all uterine tumours..
AI summary of the abstract, human-reviewed · Sep 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human · observationalMechanismReported positiveLimited evidenceTier 3 · early humann = 11
Histopathology · Apr 2026 · case series
ovarian Sertoli-Leydig cell tumorrhabdomyosarcoma (heterologous component)ovarian neoplasms
This case series of 11 ovarian Sertoli-Leydig cell tumors with heterologous rhabdomyosarcoma describes clinicopathologic features and molecular findings. All 7 tumors analyzed by next-generation sequencing had DICER1 hotspot mutations, most (6/7) also had a second loss-of-function DICER1 mutation, and additional mutually exclusive TERT promoter or TP53 alterations were observed. Component-specific sequencing in two cases showed shared DICER1 hotspots between SLCT and RMS components, supporting a clonal origin.
Reported effects: n_cases 11, n=11 · embryonal_RMS_count 10, n=11 · +17 more
Key findings
- We report clinicopathologic features of 11 ovarian SLCTs with heterologous RMS (positivity for desmin and myogenin);
- Ten tumors were in keeping with embryonal RMS and 1 with pleomorphic RMS.
- The patients showed a bimodal age distribution: seven patients (64%) were aged 33 years or younger (mean 20) and four patients (36%) were aged 52 years or older (mean 60).
- All tumors were unilateral.
- Eight of 11 cases (73%) contained other heterologous elements, including gastrointestinal-type mucinous epithelium (5 cases) and immature cartilage (3 cases).
- Seven of 11 cases (64%) underwent next-generation sequencing analysis.
- All tumors tested molecularly (7/7, 100%) harbored hotspot DICER1 mutations.
- Of these, six cases (86%) also carried a second nonsense or frameshift loss-of-function DICER1 mutation.
- In addition to DICER1 mutations, TERT c.-124C>T promoter (4 cases) or TP53 mutations (3 cases) were present in all cases and were mutually exclusive.
- Component-specific analysis in two cases revealed shared common DICER1 hotspot mutations in both the SLCT and RMS components, supporting a clonal origin.
- In one case, a TERT promoter c.-124C>T somatic mutation was present only in the RMS component; in the other case the TERT promoter mutation was found in both components while a BRAF p.V600E mutation was exclusive to the RMS component.
Limitations: Small sample size (11 cases).; Retrospective case series design without systematic clinical outcome data reported in the abstract.; Next-generation sequencing was performed in only a subset of cases (7/11).; Component-specific molecular analysis was limited to two cases.; The abstract does not report whether DICER1 mutations were somatic versus germline in all cases..
AI summary of the abstract, human-reviewed · Jul 2026. Describes what this study reported, not medical advice. View on PubMed
ReviewMechanismInconclusiveLimited evidenceTier 3 · early human
Advances in anatomic pathology · Jan 2026 · narrative review
gynecologic neoplasmsembryonal rhabdomyosarcomaSertoli-Leydig cell tumorpleuropulmonary blastoma-like peritoneal sarcomaadenosarcomagynandroblastomajuvenile granulosa cell tumorSertoli cell tumorDICER1-related Wilms-like uterine tumor
This narrative review summarizes how germline and somatic DICER1 mutations are associated with a range of benign and malignant gynecologic neoplasms and describes their shared morphologic features. The authors note that a germline loss-of-function DICER1 mutation is often followed by a somatic hotspot (second-hit) mutation in tumors, and they recommend that recognition of characteristic morphology should prompt genetic testing and surveillance for patients and families. The review proposes the term "DICER1-related primitive polyphenotypic neoplasm" to encompass the diverse histologic features of these tumors.
Key findings
- DICER1 is crucial for microRNA biogenesis and maturation.
- Germline DICER1 mutations are associated with increased risk of a wide range of benign and malignant neoplasms; the same tumors can also arise sporadically via somatic DICER1 mutations.
- In syndromic patients, a germline loss-of-function DICER1 mutation is usually followed by a somatic hotspot mutation in the tumor as a second hit.
- DICER1-associated gynecologic neoplasms most commonly include embryonal rhabdomyosarcoma and moderately to poorly differentiated Sertoli-Leydig cell tumor, with several less frequent tumor types also described.
- DICER1-mutant gynecologic neoplasms frequently share characteristic morphology (primitive mesenchyme, fetal-type epithelium/cartilage, rhabdomyoblastic and/or neuroectodermal differentiation, osteoid formation, and anaplasia).
- Recognition of these distinctive morphologic features should prompt consideration of DICER1-associated neoplasm and genetic testing to facilitate surveillance for patients and families.
- The morphologic spectrum of most DICER1-mutant gynecologic neoplasms appears wider than that of any known type of sarcoma.
- The authors propose the term "DICER1-related primitive polyphenotypic neoplasm" to better capture the diverse histologic features.
Limitations: Narrative review without description of systematic search or methods — potential selection bias in included reports.; No primary data or quantitative synthesis (no new experimental or cohort data presented).; Extent of evidence, frequency estimates, and outcomes are not quantified in the abstract..
Summarizes the association between DICER1 mutations and a spectrum of gynecologic tumors and highlights implications for pathologic recognition and genetic testing.
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed
Lab · in vitroMechanismReported positivePreclinical onlyTier 1 · lab
Stem cell research · Dec 2025
alveolar rhabdomyosarcoma
The authors describe a laboratory protocol to generate induced pluripotent stem cell (iPSC)-derived alveolar rhabdomyosarcoma (iARMS) cells during endothelial-directed differentiation by enforced expression of the PAX3::FOXO1 fusion. The resulting cell model is presented as a tool to study how PAX3::FOXO1 transforms endothelial progenitors into aggressive myogenic tumors.
Key findings
- Provided a protocol for generating iPSC-derived alveolar rhabdomyosarcoma cells (iARMS) during endothelial directed differentiation through enforced expression of PAX3::FOXO1 (P3F).
- The iARMS model enables dissection of how P3F mediates transformation of endothelial progenitors into aggressive myogenic tumors.
Limitations: In vitro model only; no in vivo or clinical validation reported in the abstract.; No quantitative results, sample sizes, or experimental details reported in the abstract.; Abstract describes a protocol/model but does not present functional or phenotypic metrics in this text..
AI summary of the abstract, human-reviewed · Sep 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Case reportInconclusiveLimited evidenceTier 3 · early humann = 1
Journal of cancer research and therapeutics · Oct 2025 · case report
This case report describes a 17-year-old girl with a very rare ovarian rhabdomyosarcoma. The tumor was diagnosed by imaging, pathology, and immunohistochemistry, and it came back within 3 months after surgery. The authors report that she then received VAC chemotherapy (vincristine, actinomycin D, and cyclophosphamide), and they emphasize the need for earlier diagnosis and more standardized treatment approaches.
Studied with: vincristine, actinomycin D, cyclophosphamide.
Key findings
- Imaging showed a large solid-cystic pelvic mass.
- Histopathology and immunohistochemical markers (desmin, myogenin, WT1) confirmed ovarian rhabdomyosarcoma.
- Recurrence occurred within 3 months after surgical resection.
- VAC chemotherapy was given after early relapse.
Limitations: Single-patient case report.; No control group.; No quantitative treatment outcome data reported.; Cannot determine effectiveness of VAC from this report alone.; Focus is diagnostic and descriptive rather than evaluative..
Describes a rare ovarian cancer case and subsequent chemotherapy, but does not evaluate a compound's anticancer effect in a comparative way.
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed
ReviewMechanismInconclusiveLimited evidenceTier 4 · clinical
Cancers · Sep 2025 · review
pleuropulmonary blastomaSertoli-Leydig cell tumorcystic nephromacervical embryonal rhabdomyosarcomacystic lung lesionsthyroid follicular nodular disease
This is a narrative review of DICER1 syndrome, a hereditary cancer predisposition caused by germline loss-of-function variants in DICER1 and characteristic second somatic hotspot mutations in the RNase IIIb domain. The review summarizes the range of associated benign and malignant tumors, describes DICER1's role as an endoribonuclease in RNA interference and microRNA processing, and concludes that the exact molecular mechanisms linking altered DICER1 function to tumorigenesis remain incompletely understood and require further research.
Key findings
- DICER1 syndrome is a hereditary cancer predisposition syndrome with a broad phenotype including pleuropulmonary blastoma, Sertoli-Leydig cell tumor, cystic nephroma, cervical embryonal rhabdomyosarcoma, cystic lung lesions, and thyroid follicular nodular disease.
- The syndrome is caused by loss-of-function germline variants in the DICER1 gene and DICER1-related tumors commonly have second somatic hotspot variants in the RNase IIIb domain.
- DICER1 encodes an endoribonuclease important for RNA interference and microRNA biogenesis.
- The review highlights gaps in knowledge about the precise molecular mechanisms by which altered DICER1 function contributes to tumorigenesis and calls for more research.
Limitations: Narrative review without original experimental or patient-level data.; Conclusions limited by existing incomplete knowledge of molecular mechanisms as noted by the authors.; Review methodology is not described in the abstract (e.g., not specified as a systematic review), so selection bias in covered literature is possible..
AI summary of the abstract, human-reviewed · Jul 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
ReviewMechanismInconclusiveModerate evidenceTier 4 · clinical
Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society · Jul 2025 · narrative review
pleuropulmonary blastomaSertoli-Leydig cell tumorcystic nephromauterine cervical embryonal rhabdomyosarcomathyroid follicular nodular disease
This narrative review summarizes the spectrum of benign and malignant tumors associated with germline heterozygous pathogenic DICER1 variants and emphasizes DICER1's role in miRNA processing and RNA interference. It highlights the most prevalent tumor types (pleuropulmonary blastoma, Sertoli-Leydig cell tumor, cystic nephroma, uterine cervical embryonal rhabdomyosarcoma, and thyroid follicular nodular disease), notes that these neoplasms are rare and often occur in children, and focuses on their histological features and molecular pathogenesis. The authors recommend that pathologists consider additional molecular testing and referral for genetic counseling and testing to facilitate earlier diagnosis.
Key findings
- DICER1 syndrome is caused by germline heterozygous pathogenic variants in DICER1 and is essential in miRNA processing and RNA interference.
- The syndrome is heterogeneous and includes a large variety of benign and malignant tumor types.
- The most prevalent tumor types include pleuropulmonary blastoma, Sertoli-Leydig cell tumor, cystic nephroma, uterine cervical embryonal rhabdomyosarcoma, and thyroid follicular nodular disease.
- These neoplasms are rare and particularly occur in the pediatric population.
- Pathologists should be aware of the potential relationship to DICER1 syndrome to perform or suggest additional molecular pathologic analysis and refer patients and their parents for genetic counseling and testing.
- The review emphasizes histological features of DICER1-related tumors and reflects on DICER1 molecular pathogenesis to raise awareness and facilitate earlier diagnosis.
Limitations: Review article that does not present new primary data.; Rarity of the tumor types limits the available evidence base and generalizability.; Focus is on histological features and molecular pathogenesis; the review does not provide primary clinical outcome or treatment data..
AI summary of the abstract, human-reviewed · Jul 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human · observationalMixed resultsLimited evidenceTier 3 · early humann = 6
Cureus · Jun 2025 · retrospective analysis
ovarian rhabdomyosarcoma
This retrospective case series reviewed six pediatric patients with ovarian rhabdomyosarcoma treated over a 25-year period at a national cancer center in Peru. Most tumors had embryonal histology, four patients presented with distant metastases (stage/group IV), none tested positive for fusion genes, and all received chemotherapy plus surgery with efforts to preserve fertility when appropriate. Three patients received abdominopelvic radiotherapy (2,400 cGy in 16 sessions); one low-risk patient survived up to 94 months and the authors report multimodal treatment produced survival exceeding 87 months in some cases.
Reported effects: number of patients 6, n=6 · abdominopelvic radiotherapy total dose 2400, n=3 · +3 more
Key findings
- Six female patients aged between five months and 13 years were included.
- Four patients were classified as clinical stage/group IV due to distant metastases; two were low-risk.
- The majority had embryonal histology and none tested positive for fusion genes.
- All patients underwent chemotherapy and surgery; surgical approaches emphasized fertility preservation and varied by disease extent.
- Three patients received intensity-modulated abdominopelvic radiotherapy at a total dose of 2,400 cGy delivered in 16 sessions for peritoneal sarcomatosis (two for persistent disease after chemotherapy and surgery, one for high-risk histology).
- One low-risk patient achieved a survival of up to 94 months.
- Authors conclude ovarian rhabdomyosarcoma is rare, presents with nonspecific clinical/radiologic features, immunohistochemistry is essential for diagnosis, and multimodal treatment can achieve long-term survival, including in metastatic cases.
Limitations: Very small sample size (n=6).; Retrospective, single-center design increases risk of selection and reporting bias.; Heterogeneous disease stages and treatments among patients limit generalizability.; Limited outcome detail reported for individual patients (only one specific long-term survival reported).; No control or comparison group and no standardized prospective follow-up reported.; Molecular/genetic testing beyond fusion-gene negativity is not described in the cohort..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text