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New targeted treatments for advanced sarcomas.
Li, Chia-Chen; Chen, Tom Wei-Wu.
Afiliação
  • Li CC; Department of Medical Oncology, National Taiwan University Cancer Center.
  • Chen TW; Department of Oncology, National Taiwan University Hospital.
Curr Opin Oncol ; 35(4): 309-314, 2023 07 01.
Article em En | MEDLINE | ID: mdl-37222206
PURPOSE OF REVIEW: The purpose of this review is to provide the rationale and results behind recent clinical trials regarding molecular-targeted agents for advanced sarcomas. RECENT FINDINGS: Tazemetostat, a first-in-class EZH2 inhibitor, was approved to treat advanced epithelioid sarcoma. In synovial sarcoma, the interaction between pathognomonic SS18-SSX fusion protein and the BAF complex has brought insight in using BRD9 inhibitors as a treatment based on synthetic lethality. MDM2 overexpression is an important mechanism to suppress p53 function, and MDM2 gene amplification is pathognomonic in well differentiated and dedifferentiated liposarcoma. Two MDM2 inhibitors, milademetan and BI907828, have both reached the optimal dosing and have shown promising efficacy in MDM2-amplified liposarcoma. Late-stage pivotal studies are ongoing for both of these MDM2 inhibitors. The co-amplification of CDK4 and MDM2 in liposarcoma also provided a rationale for CDK4/6 inhibitors as a potential therapy. Selinexor, an exportin-1 inhibitor, has shown single-agent activity in dedifferentiated liposarcoma and action in gastrointestinal stromal tumour in combination with imatinib. Lastly, a new formulation of mTOR inhibitor, nab-sirolimus, was recently approved for perivascular epithelioid cell tumour (PEComa). SUMMARY: Molecular-guided precision medicine holds a bright future in bringing more active treatments for advanced sarcoma patients.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sarcoma / Lipossarcoma / Antineoplásicos Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sarcoma / Lipossarcoma / Antineoplásicos Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article