^
3d
CRISPR-Cas9-Mediated Bioluminescent Tagging of Endogenous Proteins by Fluorescent Protein-Assisted Cell Sorting. (PubMed, Methods Mol Biol)
However, oncogenic fusions involving transcription factors such as PAX3-FOXO1 in alveolar fusion gene-positive rhabdomyosarcoma (FP-RMS) have been difficult to inhibit due to the apparent lack of tractable drug-like binding sites comparable to that recognized by Gleevec (imatinib mesylate) on the BCR-ABL1 tyrosine kinase fusion protein...To facilitate single-cell clonal isolation of knock-ins, the homology-directed repair template encoding HiBiT was followed by a P2A self-cleaving peptide for coexpression of an mCherry fluorescent protein as a fluorescence-activated cell sorter (FACS)-selectable marker. HiBiT tagging thus allows highly sensitive luminescence detection of endogenous PAX3-FOXO1 levels permitting quantitative high-throughput screening of large compound libraries for the discovery of PAX3-FOXO1 inhibitors and degraders.
Journal
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • FOXO1 (Forkhead box O1) • PAX3 (Paired Box 3)
|
PAX3-FOXO1 fusion
|
imatinib
9d
Unraveling the Clinicopathological Diversity and Subtypes of Rhabdomyosarcoma: A Study From a Tertiary Care Center. (PubMed, Cureus)
Our findings underscore the unique presentation of RMS in adults, with trunk and genitourinary tracts emerging as primary sites and alveolar and pleomorphic RMS observed as the predominant histological subtypes. Furthermore, the study sheds light on rare subtypes with distinct anatomical distributions.
Journal
|
VIM (Vimentin) • MYOD1 (Myogenic Differentiation 1)
9d
A Rare Case Report of Intraosseous Spindle and Epithelioid Rhabdomyosarcoma With TFCP2 Rearrangement: A Pathological Diagnostic Conundrum and Literature Review. (PubMed, Int J Surg Pathol)
Therefore, we summarized the clinicopathological, immunohistochemical, and molecular alterations of 43 cases of this rare rhabdomyosarcoma variant in the English-language literature. In addition, the differential diagnosis of this lesion is crucial either.
Review • Journal
|
TFCP2 (Transcription Factor CP2)
9d
P53 Overexpression May Represent an Early Marker of Clinicopathologic Progression in Vasculogenic Mesenchymal Lesions of Germ Cell Tumor Origin. (PubMed, Virchows Arch)
P53 overexpression is associated with disease progression in a subset of VMTs and may precede morphologic transformation to sarcoma. Routine evaluation of VMTs with p53 IHC seems justified, with overexpressors likely requiring an close clinical surveillance.
Journal
|
TP53 (Tumor protein P53)
|
TP53 overexpression
9d
Busulfan, Melphalan, Topotecan Hydrochloride, and a Stem Cell Transplant in Treating Patients With Newly Diagnosed or Relapsed Solid Tumor (clinicaltrials.gov)
P1, N=25, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024
Trial completion date • Metastases
|
topotecan • melphalan • busulfan • Neupogen (filgrastim)
11d
Transforming Growth Factor Beta and Alveolar Rhabdomyosarcoma: A Challenge of Tumor Differentiation and Chemotherapy Response. (PubMed, Int J Mol Sci)
We next highlight current chemotherapy strategies, including a combination of the FDA-approved drugs vincristine, actinomycin D, and cyclophosphamide (VAC); cabozantinib; bortezomib; vinorelbine; AZD 1775; and cisplatin. Lastly, we discuss chemotherapy agents that target the differentiation of tumor cells in ARMS, which include all-trans retinoic acid (ATRA) and 5-Azacytidine. Improving our understanding of the role of signaling pathways, such as TGF-β1, in the development of ARMS tumor cells differentiation will help inform more tailored drug administration in the future.
Review • Journal
|
TGFB1 (Transforming Growth Factor Beta 1) • PAX3 (Paired Box 3) • PAX7 (Paired Box 7)
|
cisplatin • bortezomib • azacitidine • Cabometyx (cabozantinib tablet) • cyclophosphamide • adavosertib (AZD1775) • vincristine • vinorelbine tartrate • dactinomycin
15d
Statin-Sensitive Akt1/Src/Caveolin-1 Signaling Enhances Oxidative Stress Resistance in Rhabdomyosarcoma. (PubMed, Cancers (Basel))
We found that treatment with cholesterol-lowering drugs such as lovastatin and simvastatin promoted cell apoptosis in all RMS lines by reducing Akt1 and Cav1 levels and increasing intracellular ROS levels...Furthermore, in combination with the chemotherapeutic agent actinomycin D, statins were effective in reducing cell survival through increased apoptosis. Taken together, our findings suggest that the molecularly linked signature formed by Akt1, Src, Cav1, and catalase may represent a prognostic determinant for identifying subgroups of RMS patients with higher probability of recurrence after radiotherapy. Furthermore, statin-induced oxidative stress could represent a treatment option to improve the success of radiotherapy.
Journal
|
AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CAV1 (Caveolin 1) • CAT (Catalase)
|
dactinomycin • simvastatin • lovastatin
15d
CIRCULATING TUMOR DNA IS DETECTABLE AT RELAPSE IN FIVE PEDIATRIC PATIENTS WITH SOLID TUMORS (ASPHO 2024)
In our study, the Signatera ctDNA assay was a reliable reflection, or even predictor, of relapse or progression in five pediatric patients with solid tumors. Further investigation is needed to validate the reliability and best utility of this test. This study was supported by the Natera early adopter program.
Clinical • Circulating tumor DNA
|
Signatera™
16d
Evaluation of the role of AXL in fusion-positive pediatric rhabdomyosarcoma identifies the small-molecule inhibitor bemcentinib (BGB324) as potent chemosensitizer. (PubMed, Mol Cancer Ther)
Instead, pharmacological blockade with the AXL inhibitors bemcentinib (BGB324), cabozantinib and NPS-1034 rapidly killed RMS cells in an AXL-independent manner, and augmented the efficacy of the chemotherapeutics vincristine and cyclophosphamide. In vivo administration of the combination of bemcentinib and vincristine exerted strong anti-tumoral activity in a rapidly progressing PDX mouse model, significantly reducing tumor bruden compared to single-agent treatment. Collectively, our data identify bemcentinib as a promising drug to improve chemotherapy efficacy in RMS patients.
Journal
|
AXL (AXL Receptor Tyrosine Kinase)
|
AXL overexpression
|
Cabometyx (cabozantinib tablet) • cyclophosphamide • bemcentinib (BGB324) • vincristine
16d
Trial completion
|
HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • HLA-DQB1 (Major Histocompatibility Complex, Class II, DQ Beta 1) • HLA-B (Major Histocompatibility Complex, Class I, B) • HLA-C (Major Histocompatibility Complex, Class I, C)
23d
Evolution of clinically relevant variants in advanced pediatric sarcomas (AACR 2024)
Interestingly, in three cases there was emergence of a new variant activating the RAF/MAPK or AKT pathway.Conclusion Pediatric sarcomas display a range of genomic changes over time. Given the observed changes in oncogenic alterations, there may be utility to repeat sequencing of relapsed tumor biopsies to understand these changes.
Clinical • Metastases
|
TP53 (Tumor protein P53) • STAG2 (Stromal Antigen 2)
|
OncoPanel™ Assay
26d
ARST2031: A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High Risk Rhabdomyosarcoma (clinicaltrials.gov)
P3, N=118, Recruiting, Children's Oncology Group | Trial completion date: Dec 2027 --> Sep 2027 | Trial primary completion date: Dec 2027 --> Sep 2027
Trial completion date • Trial primary completion date
|
FOXO1 (Forkhead box O1)
|
cyclophosphamide • vincristine • dactinomycin • Navelbine oral (vinorelbine tartrate oral)
26d
NCI-2019-08556: Nivolumab and BO-112 Before Surgery for the Treatment of Resectable Soft Tissue Sarcoma (clinicaltrials.gov)
P1, N=14, Active, not recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2024 --> Jan 2025
Trial completion date • Trial primary completion date • Surgery
|
Opdivo (nivolumab) • polyinosinic:polycytidylic acid (BO-112)
27d
Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors (clinicaltrials.gov)
P1/2, N=128, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=184 --> 128
Enrollment closed • Enrollment change
|
EWSR1 (EWS RNA Binding Protein 1) • FUS (FUS RNA Binding Protein)
|
Ibrance (palbociclib) • temozolomide • cyclophosphamide • irinotecan • topotecan
28d
KDM3B inhibitors disrupt the oncogenic activity of PAX3-FOXO1 in fusion-positive rhabdomyosarcoma. (PubMed, Nat Commun)
Thus, we report KDM inhibitors P3FI-63 and P3FI-90 with the highest specificity for KDM3B. Their potent suppression of PAX3-FOXO1 activity indicates a possible therapeutic approach for FP-RMS and other transcriptionally addicted cancers.
Journal
|
FOXO1 (Forkhead box O1) • PAX3 (Paired Box 3)
|
PAX3-FOXO1 fusion
30d
Evaluation of TRIM63 RNA in situ hybridization (RNA-ISH) as a potential biomarker for alveolar soft-part sarcoma (ASPS). (PubMed, Med Oncol)
Staining was also identified in tumors with known subsets characterized by TFE3 alterations such as perivascular epithelioid cell neoplasm (PEComa, average H-score 228), while tumors known to exhibit overexpression of TFE3 protein without cytogenetic alterations, such as melanoma and granular cell tumor, generally showed less TRIM63 ISH staining (average H-scores 147 and 96, respectively). Quantitative assessment of TRIM63 staining by RNA-ISH is potentially a helpful biomarker for tumors with molecular TFE3 alterations such as ASPS.
Journal
|
TFE3 • ASPSCR1 (ASPSCR1 Tether For SLC2A4) • CTSK (Cathepsin K) • MITF (Melanocyte Inducing Transcription Factor)
|
TFE3 fusion
30d
Adult-onset cancer predisposition syndromes in children and adolescents - to test or not to test? (PubMed, Clin Cancer Res)
However, germline panel testing is increasingly being performed in children and adolescents with cancer, and exome and genome sequencing may be offered more commonly in this population in the future. The precise pediatric cancer risks and spectra associated with PVs in aoCPGs, underlying cellular mechanisms and somatic mutational signatures, as well as treatment response, second neoplasm risks and psycho-oncological aspects require further research.
Journal • BRCA Biomarker
|
BRCA2 (Breast cancer 2, early onset) • BARD1 (BRCA1 Associated RING Domain 1)
|
MSI-H/dMMR
1m
Auto Transplant for High Risk or Relapsed Solid or CNS Tumors (clinicaltrials.gov)
P=N/A, N=44, Completed, Masonic Cancer Center, University of Minnesota | Recruiting --> Completed | N=20 --> 44
Trial completion • Enrollment change
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CD34 (CD34 molecule)
|
LDH elevation • MYCN amplification • MYCN expression
|
carboplatin • paclitaxel • ifosfamide • etoposide IV • melphalan • thiotepa • busulfan
1m
New P2 trial
|
doxorubicin hydrochloride • ifosfamide
1m
Reappraisal of prognostic factors used in the European Pediatric Soft Tissue Sarcoma Study Group RMS 2005 study for localized rhabdomyosarcoma to optimize risk stratification and generate a prognostic nomogram. (PubMed, Cancer)
The results presented here provide the rationale to modify the EpSSG stratification, with the most significant change represented by the replacement of histology with fusion status. This classification was adopted in the new international trial launched by the EpSSG.
Journal
|
FOXO1 (Forkhead box O1)
1m
Molecular characterization of ANKRD1 in rhabdomyosarcoma cell lines: expression, localization, and proteasomal degradation. (PubMed, Histochem Cell Biol)
We have shown that RMS cells are not able to overexpress ANKRD1 protein, which can be attributed to its proteasomal degradation. The unsuccessful attempt to overexpress ANKRD1 in RMS cells indicates the possibility that its overexpression may have detrimental effects for RMS cells and opens a window for further research into its role in RMS pathogenesis and for potential therapeutic targeting.
Preclinical • Journal
|
ANKRD1 (Ankyrin Repeat Domain 1)
|
ANKRD1 overexpression
1m
Angiosarcoma of the head and neck: A clinicopathologic study with special emphasis on diagnostic pitfalls. (PubMed, Indian J Pathol Microbiol)
Head and neck AS pose a significant diagnostic challenge due to their broad morphologic spectrum. Proper clinicopathologic correlation is necessary to avoid misdiagnosis.
Journal
|
CD34 (CD34 molecule) • CD31 (Platelet and endothelial cell adhesion molecule 1) • PECAM1 (Platelet And Endothelial Cell Adhesion Molecule 1)
|
CD34 positive
1m
Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors (clinicaltrials.gov)
P1/2, N=184, Recruiting, Pfizer | Trial primary completion date: Feb 2024 --> Aug 2024 | Phase classification: P2 --> P1/2
Phase classification • Trial primary completion date • Combination therapy
|
EWSR1 (EWS RNA Binding Protein 1) • FUS (FUS RNA Binding Protein)
|
Ibrance (palbociclib) • temozolomide • cyclophosphamide • irinotecan • topotecan
1m
Primary Sarcomas of the Bladder (Bsarc) and Prostate (Psarc): A Genomic Landscape Study (USCAP 2024)
GA in TP53, ATRX and RB1 were the most common GA identified in Bsarc and Psarc. Bsarc have more than 2-fold more GA compared to Psarc. Further study of both Bsarc and Psarc designed to further subclassify and design novel treatment for these rare tumors appears warranted.
Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • ATRX (ATRX Chromatin Remodeler) • TSC2 (TSC complex subunit 2) • BCOR (BCL6 Corepressor) • ERG (ETS Transcription Factor ERG) • TMPRSS2 (Transmembrane serine protease 2) • FLCN (Folliculin) • STAT6 (Signal transducer and activator of transcription 6) • NAB2 (NGFI-A Binding Protein 2)
|
PD-L1 expression • PTEN mutation • TMPRSS2-ERG fusion • FLCN mutation
|
PD-L1 IHC 22C3 pharmDx
1m
Biological Characterisation of High Risk CHildhood Cancer in Children, Adolescents and Young Adults (MICCHADO) (clinicaltrials.gov)
P=N/A, N=600, Recruiting, Institut Curie | Trial primary completion date: Sep 2026 --> Apr 2027
Trial primary completion date
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
1m
Collecting and Storing Tissue From Young Patients With Cancer (clinicaltrials.gov)
P=N/A, N=213, Recruiting, Children's Oncology Group | Trial primary completion date: Dec 2023 --> Dec 2024
Trial primary completion date
1m
RMS-AJA-1701: Clinico-biological Study/Characterization of Rhabdomyosarcoma in Adolescents and Young Adults, 15-25-year-old Patients (clinicaltrials.gov)
P=N/A, N=113, Active, not recruiting, Centre Oscar Lambret | Trial completion date: Jun 2023 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2024
Trial completion date • Trial primary completion date
|
MYOD1 (Myogenic Differentiation 1)
1m
International PPB/DICER1 Registry (clinicaltrials.gov)
P=N/A, N=3400, Recruiting, Children's Hospitals and Clinics of Minnesota | Trial completion date: Dec 2028 --> Dec 2035 | Trial primary completion date: Dec 2025 --> Dec 2030
Trial completion date • Trial primary completion date
|
DICER1 (Dicer 1 Ribonuclease III)
|
doxorubicin hydrochloride • cyclophosphamide
1m
Genetic Mutational Analysis of Saliva or Buccal Mucosa Samples From Patients With Embryonal or Alveolar Rhabdomyosarcoma (clinicaltrials.gov)
P=N/A, N=900, Active, not recruiting, Children's Oncology Group | Trial completion date: Dec 2023 --> Dec 2024
Trial completion date
1m
Trial completion date • Surgery
|
doxorubicin hydrochloride • Votrient (pazopanib) • cyclophosphamide • ifosfamide • daunorubicin
1m
Phase I Study of Olaparib and Temozolomide for Ewings Sarcoma or Rhabdoomyosarcoma (clinicaltrials.gov)
P1, N=93, Active, not recruiting, Massachusetts General Hospital | Recruiting --> Active, not recruiting | Trial completion date: Jul 2024 --> Dec 2024 | Trial primary completion date: Jul 2022 --> Nov 2024
Enrollment closed • Trial completion date • Trial primary completion date • Metastases
|
Lynparza (olaparib) • temozolomide • irinotecan
1m
Enrollment open
|
doxorubicin hydrochloride • Votrient (pazopanib) • cyclophosphamide • ifosfamide • Xpovio (selinexor)
1m
Rhabdomyosarcoma of the tongue in a neonatal calf. (PubMed, J Comp Pathol)
The mass was diagnosed as embryonal rhabdomyosarcoma. To the best of our knowledge, this is the first reported case of bovine congenital lingual rhabdomyosarcoma, which is rare in animals.
Journal
|
VIM (Vimentin) • MB (Myoglobin) • MYOD1 (Myogenic Differentiation 1)
2ms
Divergent HLA variations and heterogeneous expression but recurrent HLA loss-of- heterozygosity and common HLA-B and TAP transcriptional silencing across advanced pediatric solid cancers. (PubMed, Front Immunol)
The consequences of HLA class II expression by immune cells remain to be established. Immunogenetic profiling should be implemented in routine to inform immunotherapy trials for precision medicine of pediatric cancers.
Journal • IO biomarker • Metastases
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • HLA-B (Major Histocompatibility Complex, Class I, B)
2ms
Trial completion
|
gemcitabine • Sulanda (surufatinib)
2ms
When the second comes first- rhabdomyosarcoma preceding heritable retinoblastoma- a case report. (PubMed, BMC Ophthalmol)
Non-ocular SPTs like sarcomas are usually known to manifest in heritable rb survivors with a lag of two to three decades (earlier if exposure to radiation is present) from the presentation of the rb. However, in our case, this seemed to be reversed with the RMS being manifest at an unusual early age and the rb being diagnosed at a later point in time.
Journal
|
RB1 (RB Transcriptional Corepressor 1)
|
RB1 mutation
2ms
New P1/2 trial
|
doxorubicin hydrochloride • Votrient (pazopanib) • cyclophosphamide • ifosfamide • Xpovio (selinexor)
2ms
Histogram Analysis of Apparent Diffusion Coefficient Maps Provides Genotypic and Pretreatment Phenotypic Information in Pediatric and Young Adult Rhabdomyosarcoma. (PubMed, Acad Radiol)
Our findings demonstrate the potential of ADC histogram metrics to predict clinically relevant variables for rhabdomyosarcoma, including FOXO1 fusion status, histopathology, Clinical Group, TNM staging, and risk stratification.
Journal
|
FOXO1 (Forkhead box O1)
2ms
Enhanced Anti-Pediatric Sarcomas Effect of Everolimus with Secukinumab by Targeting IL-17A. (PubMed, Mol Cancer Ther)
Results showed that everolimus intervention had limited inhibitory effect on PDX tumor growth compared to cyclophosphamide. However, everolimus induces sarcoma cells to produce IL-17A, which promotes tumor cell survival and counteracts its anti-pediatric sarcomas effect. The combination of secukinumab effectively eliminates the effects of IL-17A, thereby improving the therapeutic efficacy of everolimus in the context of pediatric sarcomas.
Journal
|
EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1) • IL17A (Interleukin 17A)
|
everolimus • cyclophosphamide • Cosentyx (secukinumab)
2ms
Neopetrotaurines A-C, Isoquinoline Alkaloids with an Unprecedented Taurine Bridge from the Sponge Neopetrosia sp. (PubMed, J Nat Prod)
Thus, the application of LR-HSQMBC and HMBC NMR experiments optimized to detect 4- and 5-bond long-range H-C heteronuclear correlations facilitated the structure elucidation of these unusual taurine-bridged marine metabolites. Neopetrotaurines A-C (1-3) showed significant inhibition of transcription driven by the oncogenic fusion protein PAX3-FOXO1, which is associated with alveolar rhabdomyosarcoma, and cytotoxic activity against PAX3-FOXO1-positive cell lines.
Journal
|
PAX3 (Paired Box 3)
2ms
Anti-Angiogenic Therapy Post Transplant (ASCR) for Pediatric Solid Tumors (clinicaltrials.gov)
P1, N=14, Completed, Washington University School of Medicine | Active, not recruiting --> Completed
Trial completion
|
CD34 (CD34 molecule)
|
cyclophosphamide • thalidomide
2ms
Mosaic RASopathies concept: different skin lesions, same systemic manifestations? (PubMed, J Med Genet)
This review delineates genotype/phenotype correlations of syndromic epidermal nevi with somatic RAS and BRAF pathogenic variants and may help improve their follow-up.
Review • Journal
|
KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • HRAS (Harvey rat sarcoma viral oncogene homolog) • RAS (Rat Sarcoma Virus)