bims-myxlip Biomed News
on Myxoid liposarcoma
Issue of 2024–09–08
five papers selected by
Laura Mannarino, Humanitas Research



  1. Radiol Case Rep. 2024 Oct;19(10): 4650-4653
      Trabectedin is an antineoplastic drug used to treat soft tissue sarcomas. Trabectedin is mainly infused from the central venous port (CVP) because trabectedin leakage causes serious skin and soft tissue complications. Characteristic sterile inflammation has recently been reported after infusion of trabectedin from the CVP. Here, we report a case of sterile inflammation along a tunneled catheter pathway after trabectedin infusion from the CVP, with residual postinflammatory changes even after CVP removal. A 57-year-old man with myxoid liposarcoma developed skin erythema, swelling, and induration along a tunneled catheter pathway of the CVP after 16 cycles of trabectedin infusion through the CVP. The patient was diagnosed with sterile inflammation because various tests were negative for infection. The CVP was removed because the increasing injection resistance made trabectedin infusion difficult. The catheter firmly adhered to the surrounding tissue during removal. The induration and pigmentation along the catheter persisted for 4 months after CVP removal.
    Keywords:  Central venous port; Sterile inflammation; Trabectedin
    DOI:  https://doi.org/10.1016/j.radcr.2024.07.047
  2. Front Pharmacol. 2024 ;15 1411707
      Background: Trabectedin is an antineoplastic drug approved for patients (pts) with advanced soft tissue sarcomas (STS). Interestingly, the radiological evaluation of response during trabectedin therapy is peculiar. Methods: The aim of this single-center retrospective study is to analyze the concordance of response assessment according to RECIST compared with Choi criteria in patients with STS treated with trabectedin between 2009 and 2020 at Regina Elena National Cancer Institute in Rome. Results: We present the preliminary data collected in the last 2 months (mos) on 37 pts who received the diagnosis between 2015 and 2020, with a median age of 52.5 years (range 32-78). The median number of trabectedin cycles administered was four (range 2-50) for a median follow up of 5.83 months (range 1-60). Histological subtypes of STS were five (13.5%) leiomyosarcoma, 14 (37.8%) liposarcoma, nine (24.3%) undifferentiated pleomorphic sarcoma, three (8.1%) synovial sarcoma, and six (16.2%) other rare histological subtypes. Eight pts (21.6%) received trabectedin in the first line setting, 21 (56.8%) in the second line, and seven (18.9%) received it in subsequent lines. One pt received trabectedin as neoadjuvant therapy in a clinical trial (ISG-STS 1001). Median progression-free survival was 3.6 months (CI95% 2.7-4.6); median overall survival was 34.3 months (CI95% 0-75.4). The radiological responses were evaluated with both RECIST and Choi criteria; responses matched in 33 pts (89.2%) but not in four (10.8%). The best responses obtained according to RECIST criteria were two (5.4%) partial response (PR), 13 (35.1%) stable disease (SD), and 22 (59.5%) progressive disease (PD). Instead, two (5.4%), 13 (35.1%), and 22 (59.5%) pts obtained PR, SD, and PD respectively, according to Choi criteria. Cohen's kappa coefficient of concordance was 0.792 (p-value <0.002). A specialized radiologist performed all imaging examinations using a dedicated workstation in the same center. Conclusion: In this first analysis, the concordance between RECIST and Choi assessments demonstrates no statistically significant difference. Responses did not match for four pts. We are expanding the analysis to all pts included in the original cohort to confirm or deny these initial results.
    Keywords:  real-life; response assessment; sarcoma; soft tissue; trabectedin
    DOI:  https://doi.org/10.3389/fphar.2024.1411707
  3. Asian J Surg. 2024 Aug 30. pii: S1015-9584(24)01865-7. [Epub ahead of print]
      
    DOI:  https://doi.org/10.1016/j.asjsur.2024.08.125
  4. Clin Cancer Res. 2024 Aug 29.
       PURPOSE: 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.
    EXPERIMENTAL DESIGN: Immunohistochemical evaluation of the cell cycle regulator WEE1 was performed in a large cohort of MLS specimens. FUS::DDIT3 dependency and biological function of the G1/S cell cycle checkpoint were analyzed in a mesenchymal stem cell model and liposarcoma cell lines in vitro. WEE1 activity was modulated by RNAi‑mediated knockdown and the small molecule inhibitor MK-1775 (Adavosertib). An established MLS cell line-based chicken chorioallantoic membrane model was employed for in vivo confirmation.
    RESULTS: 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 survival in vitro and in 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.
    CONCLUSIONS: Our preclinical study identifies WEE1-mediated replication stress tolerance as molecular vulnerability in FUS::DDIT3-driven MLS tumorigenesis that could represent a novel target for therapeutic intervention.
    DOI:  https://doi.org/10.1158/1078-0432.CCR-24-1152
  5. J Hematol Oncol. 2024 Sep 02. 17(1): 76
      Soft tissue sarcomas (STS) have long been a formidable challenge in oncology, partly because of their rarity and diversity, which complicates large-scale studies and slows the advent of new treatments. Traditionally anchored by anthracycline-based chemotherapy, the landscape of STS treatment hasn't shifted dramatically in the past twenty years. However, recent strides in research are starting to paint a more hopeful picture. Leveraging advanced molecular profiling, researchers are now tailoring treatments to the unique genetic makeup of tumors, with targeted therapies showing promise. Innovations such as NTRK inhibitors for NTRK-rearranged sarcomas and gamma-secretase inhibitors for desmoid tumors are changing clinical practices. The rise of immunotherapy, including novel agents like LAG-3 inhibitors and bifunctional proteins that target both TGF-β and PD-L1, offers new avenues for treatment, particularly when combined with traditional therapies like chemotherapy. Meanwhile, the approval of epigenetic treatments for specific sarcoma subtypes heralds a new wave of strategy based on histological specificity, which could lead to more personalized and effective care. While challenges remain, the field of STS treatment is evolving, driven by a deeper understanding of the disease's biological underpinnings and a commitment to innovative research approaches.
    Keywords:  Adoptive cell transfer; Clinical trial; Combination therapy; Immunotherapy; Soft tissue sarcoma (STS); Target therapy; Tertiary lymphoid structure (TLS)
    DOI:  https://doi.org/10.1186/s13045-024-01580-3