P2, N=156, Active, not recruiting, Brigham and Women's Hospital | Recruiting --> Active, not recruiting

We found that LY2835219 and trabectedin significantly alter the nuclear distribution of endogenous EWS::FLI1, disrupting and mislocalizing EWS::FLI1 hubs, respectively. Together, our results reveal new insights into the assembly and regulation of endogenous EWS::FLI1 hubs at an unprecedented resolution. The methodology developed here will be useful for characterizing the functional hubs of many regular and pathological TFs in the future.

This multicentre study confirms that anthracycline-based regimens show activity in MCS, with responses more in line with soft tissue sarcoma than Ewing sarcoma. Their benefit in localized disease remains uncertain, but (neo)adjuvant chemotherapy with Ewing-like regimens should be considered for patients eligible for surgery. In advanced disease, trabectedin may provide prolonged disease control after anthracyclines.

P=N/A, N=10, Recruiting, West China Hospital, Sichuan University; WestVac Biopharma Co.,Ltd.

P1, N=10, Recruiting, Columbia University | Trial primary completion date: Dec 2025 --> Dec 2026

P4, N=62, Not yet recruiting, University of Sao Paulo General Hospital

Based on this, the review systematically proposes innovative immunotherapy strategies targeting this key bidirectional interaction, including blocking the recruitment of TAMs (e.g., CCL2/CCR2, CXCL12/CXCR4 inhibitors), directly eliminating TAMs (e.g., CSF1R inhibitors, bisphosphonates, trabectedin), or reprogramming them into anti-tumour M1-type (e.g., CD40 agonists, TLR agonists, CD47-SIRPα axis blockers), and emphasises the great potential of combining these TAM-targeting strategies with immune checkpoint inhibitors (e.g., anti-PD-1/PD-L1 antibodies). These combined therapies aim to synergistically enhance efficacy and overcome the current challenges of drug resistance in immunotherapy, offering new hope for more durable and effective treatment for cancer patients. Additionally, the review looks forward to the application prospects of advanced cell therapies such as nanoparticle delivery systems and chimeric antigen receptor macrophages (CAR-M) in reshaping the TME and enhancing anti-tumour immune responses, providing multi-dimensional and in-depth theoretical basis and practical directions for future cancer immunotherapy.

P2, N=40, Completed, University of Utah | Enrolling by invitation --> Completed

P2, N=100, Recruiting, Italian Sarcoma Group | Trial completion date: Dec 2025 --> Dec 2026

P1, N=20, Recruiting, University Hospital, Toulouse | Trial completion date: Oct 2025 --> Dec 2026 | Trial primary completion date: Oct 2025 --> Dec 2026

The findings indicate that rMETase can overcome ultra-high doxorubicin resistance in fibrosarcoma cells, likely through targeting methionine addiction, a universal metabolic vulnerability of cancer. These results support the potential clinical application of methionine restriction therapy to treat doxorubicin-resistant STS.

P2, N=1, Terminated, Nantes University Hospital | N=50 --> 1 | Trial completion date: Nov 2026 --> Dec 2025 | Recruiting --> Terminated | Trial primary completion date: Nov 2026 --> Dec 2025; Recruitment difficulties