MDM2 is a critical negative regulator of the p53 tumor suppressor protein. Selected sarcoma subtypes are being treated with Trabectedin in second line, which promotes DNA damage and p53-dependent apoptosis. The aim of this study was to evaluate the improvement of Trabectedin response with MDM2 inhibitors in soft tissue sarcomas. The antitumor effects of Trabectedin, Nutlin-3A and RG7112 as single agents or in combination were examined in vitro. RG7112 significantly synergized with Trabectedin in MDM2-amplified liposarcoma cells, representing a promising new therapeutic strategy for the treatment of sarcomas with MDM2 amplification.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.3109/07357907.2015.1064534 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Trabectedin enhances the antitumor effects of IL-12 in triple-negative breast cancer.
Cancer Immunol Res
January 2025
The Ohio State University, Columbus, OH, United States.
Interleukin-12 (IL-12) is a potent NK cell-stimulating cytokine, but the presence of immunosuppressive myeloid cells such as myeloid-derived suppressor cells (MDSC) can inhibit IL 12-induced NK-cell cytotoxicity. Thus, we hypothesized that trabectedin, a myeloid cell-depleting agent, would improve the efficacy of IL-12 in triple-negative breast cancer (TNBC). In vitro treatment of healthy donor NK cells with trabectedin increased expression of the activation marker CD69 and mRNA expression of T BET (Tbx21), the cytotoxic ligands TRAIL (TNFSF10) and Fas ligand (FASLG) and the dendritic cell (DC)-recruiting chemokine lymphotactin (XCL1).
View Article and Find Full Text PDFTrabectedin for L-Type Sarcoma: A Retrospective Multicenter Study.
Curr Oncol
November 2024
Department of Medical Oncology, Ege University Tilay Aktaş Oncology Hospital, 35100 Izmir, Türkiye.
(1) Background: Metastatic L-type sarcomas (liposarcoma and leiomyosarcoma) are rare and have a poor prognosis. Trabectedin is an effective agent that can be used after anthracyclines. This study was designed to evaluate the real-life effectiveness and safety of trabectedin.
View Article and Find Full Text PDFMechanism of efficacy of trabectedin against myxoid liposarcoma entails detachment of the FUS-DDIT3 transcription factor from its DNA binding sites.
J Exp Clin Cancer Res
November 2024
Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Background: The marine drug trabectedin has shown unusual effectiveness in the treatment of myxoid liposarcoma (MLPS), a liposarcoma characterized by the expression of the FUS-DDIT3 chimera. Trabectedin elicits a significant transcriptional response in MLPS resulting in cellular depletion and reactivation of adipogenesis. However, the role of the chimeric protein in the mechanism of action of the drug is not entirely understood.
View Article and Find Full Text PDFFour Cases with FUS/CHOP Fusion Gene Products Positive Myxoid Liposarcoma Responding Effectively to Trabectedin Monotherapy.
Onco Targets Ther
November 2024
Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan.
Background: Myxoid liposarcoma, a rare type of tumor, accounts for approximately 30% of all liposarcomas. Myxoid liposarcomas harboring the FUS/CHOP fusion gene have shown promising results with trabectedin in basic research and some clinical experiments. However, the efficacy and safety of trabectedin in chemotherapy-naive soft tissue sarcomas or FUS/CHOP fusion gene-positive myxoid liposarcomas have not yet been established.
View Article and Find Full Text PDFTrabectedin promotes oncolytic virus antitumor efficacy, viral gene expression, and immune effector function in models of bone sarcoma.
Mol Ther Oncol
December 2024
Center for Childhood Cancer Research, Nationwide Children's Hospital, Columbus, OH 43215, USA.
We previously reported that the DNA alkylator and transcriptional-blocking chemotherapeutic agent trabectedin enhances oncolytic herpes simplex viroimmunotherapy in human sarcoma xenograft models, though the mechanism remained to be elucidated. Here we report trabectedin disrupts the intrinsic cellular antiviral response which increases viral transcript presence in the human tumor cells. We also extended our synergy findings to syngeneic murine sarcoma models, which are poorly susceptible to virus infection.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!