FOXM1, MEK, and CDK4/6: New Targets for Malignant Peripheral Nerve Sheath Tumor Therapy.
CDK4/6
FOXM1
MEK
MPNST
sarcoma
targeted therapy
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
02 Sep 2023
02 Sep 2023
Historique:
received:
29
07
2023
revised:
28
08
2023
accepted:
31
08
2023
medline:
11
9
2023
pubmed:
9
9
2023
entrez:
9
9
2023
Statut:
epublish
Résumé
Malignant peripheral nerve sheath tumors (MPNSTs) are deadly sarcomas, which desperately need effective therapies. Half of all MPNSTs arise in patients with neurofibromatosis type I (NF1), a common inherited disease. NF1 patients can develop benign lesions called plexiform neurofibromas (PNFs), often in adolescence, and over time, some PNFs, but not all, will transform into MPNSTs. A deeper understanding of the molecular and genetic alterations driving PNF-MPNST transformation will guide development of more targeted and effective treatments for these patients. This review focuses on an oncogenic transcription factor, FOXM1, which is a powerful oncogene in other cancers but little studied in MPNSTs. Elevated expression of FOXM1 was seen in patient MPNSTs and correlated with poor survival, but otherwise, its role in the disease is unknown. We discuss what is known about FOXM1 in MPNSTs relative to other cancers and how FOXM1 may be regulated by and/or regulate the most commonly altered players in MPNSTs, particularly in the MEK and CDK4/6 kinase pathways. We conclude by considering FOXM1, MEK, and CDK4/6 as new, clinically relevant targets for MPNST therapy.
Identifiants
pubmed: 37686402
pii: ijms241713596
doi: 10.3390/ijms241713596
pmc: PMC10487994
pii:
doi:
Substances chimiques
CDK4 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinase 4
EC 2.7.11.22
Forkhead Box Protein M1
0
FOXM1 protein, human
0
Mitogen-Activated Protein Kinase Kinases
EC 2.7.12.2
CDK6 protein, human
EC 2.7.11.22
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : P30 CA086862
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS119322
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM139776
Pays : United States
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