Last update 01 Nov 2024

PAX3

Last update 01 Nov 2024

Basic Info

Synonyms

HUP2, paired box 3, Paired box protein Pax-3

+ [3]

Introduction

Transcription factor that may regulate cell proliferation, migration and apoptosis. Involved in neural development and myogenesis. Transcriptional activator of MITF, acting synergistically with SOX10 (PubMed:21965087).

Drugs associated with PAX3

PFI-90

Target

FOXO1 x KDM1A x PAX3

Mechanism

FOXO1 gene inhibitors [+2]

Active Org.

National Cancer Institute

Originator Org.

National Cancer Institute

Active Indication

Rhabdomyosarcoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PAX3

100 Translational Medicine associated with PAX3

0 Patents (Medical) associated with PAX3

1,989

Literatures (Medical) associated with PAX3

01 Nov 2024·Modern Pathology

Novel PAX3::MAML3 Fusion Identified in Alveolar Rhabdomyosarcoma, Using DNA Methylation Profiling to Expand the Genetic Spectrum of “Fusion-Positive” Cases

Article

Author: Pratilas, Christine ; Gross, John M ; Dermawan, Josephine K ; D'Almeida Costa, Felipe ; Trucco, Matteo ; Baraban, Ezra ; Mneimneh, Wadad ; Sun, Wenyue ; Barr, Frederic G ; Malik, Faizan ; Fritchie, Karen J

Alveolar rhabdomyosarcoma (ARMS) with FOXO1 gene rearrangements is an aggressive pediatric rhabdomyosarcoma subtype that is prognostically distinct from embryonal rhabdomyosarcoma and fusion-negative ARMS. Here, we report 2 cases of ARMS with PAX3::MAML3 fusions. The tumors arose in an infant and an adolescent as stage IV metastatic disease (by Children's Oncology Group staging system). Histologically, both cases were small round blue cell tumors arranged in vague nests and solid sheets that were diffusely positive for desmin and myogenin. By methylation profiling and unsupervised clustering analysis, the tumors clustered with ARMS with classic FOXO1 rearrangements and ARMS with variant PAX3::NCOA1/INO80D fusions, but not with biphenotypic sinonasal sarcoma (BSNS) with PAX3::MAML3/NCOA2/FOXO1/YAP1 fusions nor with other small round blue cell tumors, including embryonal rhabdomyosarcoma. The differentially methylated genes between ARMS and BSNS were highly enriched in genes involved in myogenesis, and 21% of these genes overlap with target genes of the PAX3::FOXO1 fusion transcription factor. On follow-up after initiation of vincristine/actinomycin/cyclophosphamide chemotherapy, the tumors showed partial and complete clinical responses, consistent with typical upfront chemotherapy responsiveness of ARMS with the classic FOXO1 rearrangement. We conclude that PAX3::MAML3 is a novel variant fusion of ARMS, which displays a methylation signature distinct from BSNS despite sharing similar PAX3 fusions. These findings highlight the utility of methylation profiling in classifying ARMS with noncanonical fusions.

01 Nov 2024·Medicinal Research Reviews

Targeted immunotherapy and nanomedicine for rhabdomyosarcoma: The way of the future

Review

Author: Morel, Victoria Judith ; Rössler, Jochen ; Bernasconi, Michele

AbstractRhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. Histology separates two main subtypes: embryonal RMS (eRMS; 60%–70%) and alveolar RMS (aRMS; 20%–30%). The aggressive aRMS carry one of two characteristic chromosomal translocations that result in the expression of a PAX3::FOXO1 or PAX7::FOXO1 fusion transcription factor; therefore, aRMS are now classified as fusion‐positive (FP) RMS. Embryonal RMS have a better prognosis and are clinically indistinguishable from fusion‐negative (FN) RMS. Next to histology and molecular characteristics, RMS risk groupings are now available defining low risk tumors with excellent outcomes and advanced stage disease with poor prognosis, with an overall survival of about only 20% despite intensified multimodal treatment. Therefore, development of novel effective targeted strategies to increase survival and to decrease long‐term side effects is urgently needed. Recently, immunotherapies and nanomedicine have been emerging for potent and effective tumor treatments with minimal side effects, raising hopes for effective and safe cures for RMS patients. This review aims to describe the most relevant preclinical and clinical studies in immunotherapy and targeted nanomedicine performed so far in RMS and to provide an insight in future developments.

01 Nov 2024·Neurochemistry International

Cycloleucine induces neural tube defects by reducing Pax3 expression and impairing the balance of proliferation and apoptosis in early neurulation

Article

Author: Wei, Kaixin ; Zhang, Li ; Ma, Huijing ; Niu, Bo ; Liu, Yurong ; Wang, Xiuwei ; Zhao, Xiaorong ; Cao, Rui ; Li, Dandan ; Zhang, Xiaona

S-adenosylmethionine (SAM) plays a critical role in the development of neural tube defects (NTDs). Studies have shown that the paired box 3 (Pax3) gene is involved in neural tube closure. However, the exact mechanism between Pax3 and NTDs induced by SAM deficiency remains unclear. Here, The NTD mouse model was induced using cycloleucine (CL), an inhibitor of SAM biosynthesis, to determine the effect of Pax3 on NTDs. The effect of CL on NTD occurrence was assessed by 5-ethynyl-2'-deoxyuridine (EdU) staining, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and Western blot in NTD embryonic brain tissues and immortalized hippocampal neuron cells (HT-22). A high incidence of NTDs was observed when CL was administered at a dose of 200 mg/kg body weight. The levels of SAM and Pax3 were significantly reduced in NTD embryonic brain tissues and HT-22 cells after CL exposure. Decreased proliferation and excessive apoptosis were observed in neuroepithelial cells of NTD embryos and HT-22 cells under SAM deficiency, but these effects were reversed by overexpression of Pax3. These results suggest that decreased expression of Pax3 impairs the dynamic balance between cellular proliferation and apoptosis, contributing to NTDs induced by SAM deficiency, which would provide new insights for clarifying the underlying mechanism of NTDs.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

PAX3

Basic Info

Related

Analysis