Myxoid Liposarcomas: Systemic Treatment Options

Nassif, Elise F.; Keung, Emily Z.; Thirasastr, Prapassorn; Somaiah, Neeta

doi:10.1007/s11864-023-01057-4

Cited by 13 publications

(7 citation statements)

References 88 publications

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“…Trabectedin is a marine-derived antitumor drug that achieves antitumor cell activity by inhibiting transcription, anti-angiogenesis, and immune regulation. Related tests show that MRCL and other translocation-related sarcomas (liposarcoma and leiomyosarcoma) are the most sensitive types of sarcoma related to trabectedin [39]. The French Sarcoma Group conducted a randomized phase III study evaluating the efficacy of trabectedin versus best supportive care (BSC) in patients with advanced STS.…”

Section: Discussionmentioning

confidence: 99%

“…Eribulin has now become an effective treatment for MRCL. Several recent trials of eribulin combined with other drugs for advanced liposarcoma have prolonged the median PFS in patients with considerable results [39]. In a phase II trial of eribulin-gemcitabine combination in patients with advanced liposarcoma, a 12-week PFS rate was 70.6% (n = 12/17) in the liposarcoma cohort, with a median PFS of 5.7 months [41].…”

Section: Discussionmentioning

confidence: 99%

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Prognostic factors and nomogram construction for primary retroperitoneal myxoid/round cell liposarcoma: an analysis of population-based data

Zhuang,

Cheng,

et al. 2024

JCTR

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Background: It has been reported that the prognosis for myxoid/round cell liposarcoma (MLPS/RCLPS) is inconsistent across different sites. However, there are neither prognostic studies nor predictive models that focused on MLPS/RCLPS of retroperitoneal origin. Methods: Utilizing the Surveillance, Epidemiology, and End Results database, we selected 171 primary retroperitoneal MLPS/RCLPS cases from the period between 2000 and 2019. Prognostic factors influencing disease-specific survival were identified through Cox regression analysis. These independent prognostic factors were then used to construct a DSS nomogram prediction model. The accuracy and reliability of this nomogram were evaluated using the concordance index (C-index) and calibration plots. Furthermore, we categorized patient prognosis using an X-tile based on the nomogram score. Results: The observed 5-year and 10-year DSS rates for all patients were 64.0% (95% CI: 56.2% – 71.8%) and 47.1% (95% CI: 38.1% – 56.1%), respectively. The patient cohort had a median age of 64 years, ranging from 24 to 92 years, with a slight male predominance (n = 92, 53.8%) over females (n = 79, 46.2%). Distant metastases were diagnosed in 24 patients (14%). The distribution of MLPS and RCLPS was 89.5% and 10.5%, respectively. In terms of treatment, adjuvant radiotherapy was administered to 33 patients (19.3%), neoadjuvant radiotherapy to 9 patients (5.3%), and chemotherapy to 20 patients (11.7%), while a significant majority (83.6%) underwent surgical procedures. Independent prognostic factors for DSS included age (HR = 1.039, P < 0.001), marital status (P = 0.029), history of previous tumors (HR = 0.257, P = 0.007), presence of metastatic disease (HR = 2.206, P = 0.027), and surgical treatment (HR = 0.490, P = 0.036). A nomogram prediction model was constructed to forecast 1-, 5-, and 10-year DSS rates, with a C-index of 0.739. Calibration plots demonstrated a strong correlation between the nomogram’s predictions and actual observations. Based on the prediction model, patients were stratified into three groups, and significant differences in prognosis were observed between these groups. Conclusion: A poorer prognosis is associated with retroperitoneal-derived MLPS/RCLPS than with other sites. The nomogram prediction model we built can be used to assist patients in consulting with their doctors and selecting patients for clinical trials. Relevance for Patients: Our study highlights the unique challenges and prognosis variations in retroperitoneal myxoid/RCLPS. The developed nomogram serves as a valuable tool for patients, aiding informed discussions with doctors and guiding decisions on treatment and clinical trial participation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prognostic factors and nomogram construction for primary retroperitoneal myxoid/round cell liposarcoma: an analysis of population-based data

Zhuang,

Cheng,

et al. 2024

JCTR

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“…TRB is applied for soft tissue sarcoma (STS) [ 26 ] and is applied in a phase III study of mesenchymal chondrosarcoma [ 27 ] as well as in a phase II study of extraskeletal myxoid chondrosarcoma. It is also used in non-operable liposarcomas and leiomyosarcomas [ 28 , 29 , 30 , 31 , 32 , 33 , 34 ] and it is applied for metastatic synovial sarcoma [ 35 , 36 ].…”

Section: Trabectedin and Lurbinectedin Uses In Oncologymentioning

confidence: 99%

Trabectedin and Lurbinectedin Modulate the Interplay between Cells in the Tumour Microenvironment—Progresses in Their Use in Combined Cancer Therapy

Povo-Retana,

Landauro-Vera,

Alvarez-Lucena

et al. 2024

Molecules

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Trabectedin (TRB) and Lurbinectedin (LUR) are alkaloid compounds originally isolated from Ecteinascidia turbinata with proven antitumoral activity. Both molecules are structural analogues that differ on the tetrahydroisoquinoline moiety of the C subunit in TRB, which is replaced by a tetrahydro-β-carboline in LUR. TRB is indicated for patients with relapsed ovarian cancer in combination with pegylated liposomal doxorubicin, as well as for advanced soft tissue sarcoma in adults in monotherapy. LUR was approved by the FDA in 2020 to treat metastatic small cell lung cancer. Herein, we systematically summarise the origin and structure of TRB and LUR, as well as the molecular mechanisms that they trigger to induce cell death in tumoral cells and supporting stroma cells of the tumoral microenvironment, and how these compounds regulate immune cell function and fate. Finally, the novel therapeutic venues that are currently under exploration, in combination with a plethora of different immunotherapeutic strategies or specific molecular-targeted inhibitors, are reviewed, with particular emphasis on the usage of immune checkpoint inhibitors, or other bioactive molecules that have shown synergistic effects in terms of tumour regression and ablation. These approaches intend to tackle the complexity of managing cancer patients in the context of precision medicine and the application of tailor-made strategies aiming at the reduction of undesired side effects.

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“…Morphologically, MLS encompass a spectrum ranging from paucicellular myxoid tumors to hypercellular round cell high-grade sarcomas associated with a more aggressive clinical course (7). Current treatment options comprise surgical excision and (neo-)adjuvant radiation and/or conventional chemotherapy to potentiate long-term survival in MLS patients (8). Although MLS demonstrates enhanced chemosensitivity, advanced or metastatic disease often translates into poor patient prognosis and therapy is administered with palliative intent (9).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exploiting WEE1 kinase activity as FUS::DDIT3-dependent therapeutic vulnerability in myxoid liposarcoma

Heinst,

Lee,

Berthold

et al. 2024

Preprint

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The pathognomonic FUS::DDIT3 fusion protein drives myxoid liposarcoma (MLS) tumorigenesis via aberrant transcriptional activation of oncogenic signaling. Since FUS::DDIT3 has so far not been pharmacologically tractable to selectively target MLS cells, this study investigated the functional role of the cell cycle regulator WEE1 as novel FUS::DDIT3-dependent therapeutic vulnerability in MLS. Here we demonstrate that enhanced WEE1 pathway activity represents a hallmark of FUS::DDIT3-expressing cell lines as well as MLS tissue specimens and that WEE1 is required for MLS cellular survivalin vitroandin vivo. Pharmacologic inhibition of WEE1 activity results in DNA damage accumulation and cell cycle progression forcing cells to undergo apoptotic cell death. In addition, our results uncover FUS::DDIT3-dependent WEE1 expression as an oncogenic survival mechanism to tolerate high proliferation and resulting replication stress in MLS. Fusion protein-driven G1/S cell cycle checkpoint deregulation via overactive Cyclin E/CDK2 complexes thereby contributes to enhanced WEE1 inhibitor sensitivity in MLS. These findings identify WEE1-mediated replication stress tolerance as molecular vulnerability in FUS::DDIT3-driven MLS tumorigenesis that could represent a novel target for therapeutic intervention.

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Myxoid Liposarcomas: Systemic Treatment Options

Cited by 13 publications

References 88 publications

Prognostic factors and nomogram construction for primary retroperitoneal myxoid/round cell liposarcoma: an analysis of population-based data

Prognostic factors and nomogram construction for primary retroperitoneal myxoid/round cell liposarcoma: an analysis of population-based data

Trabectedin and Lurbinectedin Modulate the Interplay between Cells in the Tumour Microenvironment—Progresses in Their Use in Combined Cancer Therapy

Exploiting WEE1 kinase activity as FUS::DDIT3-dependent therapeutic vulnerability in myxoid liposarcoma

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