Trabectedine

OBJECTIVE: While PLD-Trabectedin is an approved treatment for relapsed platinum-sensitive ovarian cancer, its efficacy and tolerability has so far not been tested extensively in patients who progress after poly ADP-ribose polymerase inhibitor (PARPi) treatment. METHODOLOGY: This multicenter, retrospective analysis had the objective of comparing patients receiving PLD-Trabectedin after being treated with PARP-I (cases) with PARPi-naïve patients. Descriptive and survival analyses were performed for each group...

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal neoplasms in humans, and just limited progresses have been made to extend patient survival and decrease ATC-associated mortality. Thus, the identification of novel therapeutic strategies for treating ATC is needed. Recently, our group has identified two proteins with oncogenic activity, namely HMGA1 and EZH2, with pivotal roles in ATC cancer progression. Therefore, we tested the ability of trabectedin, a HMGA1-targeting drug, and GSK126, an inhibitor of EZH2 enzymatic activity, to impair cell viability of four ATC-derived cell lines...

Of the drugs used in second-line chemotherapy for soft tissue sarcoma (STS), trabectedin is effective for liposarcoma and leiomyosarcoma (L-sarcoma), eribulin for liposarcoma, and pazopanib for non-liposarcoma. The indications for these drugs in STS other than L-sarcoma have not been established. Here we explored the prognosis, mutation profiles, and drug-response factors in STS using real-world big data. Clinicogenomic data on 1761 patients with sarcoma who underwent FoundationOne CDx were obtained from a national database in Japan...

INTRODUCTION: Clear cell sarcoma (CCS) is a rare and aggressive soft tissue sarcoma. CCS is characterized by the translocation t(12;22) (q13;q12), involving the fusion of EWSR1 and ATF1 genes, and less frequently the fusion gene EWSR1-CREB1. Usually, CCSs are considered poorly responsive to conventional chemotherapy. However, trabectedin has shown activity against translocation-related sarcomas. Furthermore, preclinical results suggest that trabectedin is a promising antitumor agent for CCS, potentially inducing melanocytic differentiation...

Pleomorphic myxoid liposarcoma (PML) is a newly recognized entity with aggressive clinical behavior and a tendency to recur. It has histological features of both myxoid and pleomorphic liposarcoma and lacks the molecular and structural chromosomal abnormalities associated with myxoid and pleomorphic liposarcoma. The data about their response to chemotherapy is quite sparse. We report a case of incidentally detected pleomorphic myxoid liposarcoma of the mediastinum in a 32-year-old gentleman. After resection and adjuvant chemotherapy with doxorubicin and ifosfamide, there was no evidence of residual disease at the end of treatment...

Stress fractures occur as a result of repeated mechanical stress on bone and are commonly found in the load-bearing lower extremities. Macrophages are key players in the immune system and play an important role in bone remodeling and fracture healing. However, the role of macrophages in stress fractures has not been adequately addressed. We hypothesize that macrophage infiltration into a stress fracture callus site promotes bone healing. To test this, a unilateral stress fracture induction model was employed in which the murine ulna of four-month-old, C57BL/6 J male mice was repeatedly loaded with a pre-determined force until the bone was displaced a distance below the threshold for complete fracture...

Despite decades of research efforts, pancreatic adenocarcinoma (PDAC) continues to present a formidable clinical challenge, demanding innovative therapeutic approaches. In a prior study, we reported the synergistic cytotoxic effects of gemcitabine and trabectedin on pancreatic cancer cells. To investigate potential mechanisms underlying this synergistic pharmacodynamic interaction, liquid chromatography-mass spectrometry-based proteomic analysis was performed, and a system pharmacodynamics model (SPD) was developed to capture pancreatic cancer cell responses to gemcitabine and trabectedin, alone and combined, at the proteome level...

BACKGROUND/AIM: The prognosis of metastatic and inoperable sarcomas is extremely poor, and intensive chemotherapy-based treatment is typically administered to prolong survival. Currently, pazopanib, eribulin, and trabectedin are key drugs used in patients with these sarcomas. The aim of the study was to identify prognostic factors for metastatic and inoperable bone and soft tissue sarcomas. PATIENTS AND METHODS: Clinicopathological data of 46 patients with metastatic and inoperable sarcomas treated with pazopanib, eribulin, and trabectedin between January 2013 and February 2022 at our institution were retrospectively analyzed...

We present the case of a 46-year-old mother of a young child who was diagnosed with metastatic leiomyosarcoma. At diagnosis, the tumor had already infiltrated the vena cava, infiltration of the pancreas was suspected, and pulmonary metastases had been histologically confirmed. The goal of treatment was to prolong survival and gain quality time for the family. When the patient had not responded to 4 cycles of doxorubicin, trabectedin was initiated. After an initial partial remission with a reduction in the size of the primary leiomyosarcoma as well as some pulmonary metastases, the disease remained stable for a total of 10 months...

Metastatic soft-tissue sarcomas (mSTS) encompass a highly heterogeneous group of rare tumours characterized by different clinical behaviours and outcomes. Currently, prognostic factors for mSTS are very limited, posing significant challenges in predicting patient survival. Within a cohort of 39 mSTS patients undergoing trabectedin treatment, it was remarkable to find one patient who underwent 73 cycles of trabectedin achieving an unforeseen clinical outcome. To identify contributing factors to her exceptional long-term survival, we have explored circulation metabolomics and biohumoral biomarkers to uncover a potential distinct host biochemical phenotype...

The therapeutic approach of pleomorphic liposarcoma (PLPS), a rare high-grade subgroup of soft tissue sarcoma, is commonly extrapolated from the management of other LPS subtypes. Only published retrospective data on PLPS currently serve as a guide for oncologists without clear recommendations or specific guidelines. In the advanced setting, specific systemic therapy such as eribulin and trabectedin showed promising activity in comparison to conventional therapy (doxorubicin- and gemcitabine-based protocols), which currently remains the current standard of care at initial stages of the disease...

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Soft tissue sarcomas (STSs) are rare malignant tumors that are difficult to prognosticate using currently available instruments. Omics sciences could provide more accurate and individualized survival predictions for patients with metastatic STS. In this pilot, hypothesis-generating study, we integrated clinicopathological variables with proton nuclear magnetic resonance (1 H NMR) plasma metabolomic and lipoproteomic profiles, capturing both tumor and host characteristics, to identify novel prognostic biomarkers of 2-year survival...

In recent years, the central role of cell bioenergetics in regulating immune cell function and fate has been recognized, giving rise to the interest in immunometabolism, an area of research focused on the interaction between metabolic regulation and immune function. Thus, early metabolic changes associated with the polarization of macrophages into pro-inflammatory or pro-resolving cells under different stimuli have been characterized. Tumor-associated macrophages are among the most abundant cells in the tumor microenvironment; however, it exists an unmet need to study the effect of chemotherapeutics on macrophage immunometabolism...

UNLABELLED: Multicellular spheroids comprised of malignant cells, endothelial cells, and mesenchymal stem cells served as an in vitro model of human solid tumors to investigate the potentiation of DNA-damaging drugs by pharmacologic modulation of DNA repair pathways. The DNA-damaging drugs, topotecan, trabectedin, and temozolomide were combined with varied inhibitors of DNA damage response enzymes including PARP (olaparib or talazoparib), ATM (ataxia telangiectasia mutated; AZD-1390), ATR (ataxia telangiectasia and Rad3-related protein; berzosertib or elimusertib), and DNA-PK (DNA-dependent protein kinase; nedisertib or VX-984)...

Objective: Trabectedin is an anti-cancer drug commonly used for the treatment of patients with metastatic soft tissue sarcoma (mSTS). Despite its recognized efficacy, significant variability in pharmacological response has been observed among mSTS patients. To address this issue, this pharmacometabolomics study aimed to identify pre-dose plasma metabolomics signatures that can explain individual variations in trabectedin pharmacokinetics and overall clinical response to treatment. Methods: In this study, 40 mSTS patients treated with trabectedin administered by 24 h-intravenous infusion at a dose of 1...

Despite the low incidence of soft tissue sarcomas (STSs), hundreds of thousands of new STS cases are diagnosed annually worldwide, and approximately half of them eventually progress to advanced stages. Currently, chemotherapy is the first-line treatment for advanced STSs. There are difficulties in selecting appropriate drugs for multiline chemotherapy, or for combination treatment of different STS histological subtypes. In this study, we first comprehensively reviewed the efficacy of various chemotherapeutic drugs in the treatment of STSs, and then described the current status of sensitive drugs for different STS subtypes...

BACKGROUND: In addition to specifically inducing tumor cell apoptosis, recombinant tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has also been reported to influence the cancer immune microenvironment; however, its underlying effects and mechanisms remain unclear. Investigating the immunomodulatory effects and mechanisms of recombinant TRAIL in the tumor microenvironment (TME) may provide an important perspective and facilitate the exploration of novel TRAIL strategies for tumor therapy...

Synovial sarcoma (SyS) is a rare aggressive soft tissue sarcoma carrying the chromosomal translocation t(X;18), encoding the fusion transcript SS18::SSX. The fusion oncoprotein interacts with both BAF enhancer complexes and polycomb repressor complexes, resulting in genome-wide epigenetic perturbations and a unique altered genetic signature. Over 80% of the patients are initially diagnosed with localized disease and have a 5-year survival rate of 70-80%, but metastatic relapse occurs in 50% of the cases. Advanced, unresectable, or metastatic disease has a 5-year survival rate below 10%, representing a critical issue...

Epithelial ovarian cancer (EOC) is the most common and fatal subtype of ovarian malignancies, with no effective therapeutics available. Our previous studies have demonstrated extraordinary suppressive efficacy of enterolactone (ENL) on EOC. A chemotherapeutic agent, trabectedin (Trabe), is shown to be effective on ovarian cancer, especially when combined with other therapeutics, such as pegylated liposomal doxorubicin or oxaliplatin. Thrombospondin 1 (THBS1), a kind of matrix glycoprotein, plays important roles against cancer development through inhibiting angiogenesis but whether it is involved in the suppression of EOC by ENL or Trabe remains unknown...