P=N/A, N=7, Terminated, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Completed --> Terminated; The study was terminated prematurely due to slow recruitment after inclusion of 7 patients (of initially planned 100 patients).

Bulk and single-cell RNAseq followed by functional validation and in silico analysis showed that CLF treatment is associated with apoptosis, ER stress, oxidative phosphorylation, and mitochondrial dysfunction. Most importantly, CLF modulates the expression of several non-coding RNAs, including MALAT1 and NEAT1, that are linked to tumor cell proliferation, cell migration, and drug resistance.

Trabectedin demonstrates low disease control rate in translocation-related sarcomas, including few MCS cases. Anti-angiogenic tyrosine kinase inhibitors, such as apatinib and pazopanib, demonstrate activity in chondrosarcoma, but MCS-specific data are lacking. IDH1 inhibition benefits conventional subtypes rather than MCS. Early immunotherapy experience is limited, but pathway-directed strategies targeting BCL2 and PI3K-mTOR warrant evaluation.

P3, N=550, Completed, Italian Sarcoma Group | Active, not recruiting --> Completed

P2, N=16, Recruiting, Italian Sarcoma Group | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Aug 2025 --> Dec 2025

P1, N=1, Enrolling by invitation, Vancouver Coastal Health

The chemotherapy combination was overall well tolerated, with good preservation of patients' quality of life, and no life-threatening adverse events reported.This descriptive case series of trabectedin-irinotecan in DSRCT supports preclinical evidence of synergistic activity. The regimen was well tolerated and showed potential clinical benefit even in heavily pre-treated patients, providing a rationale for further studies to optimize dosing and explore early integration.

Recently, our laboratory reported the dephosphorylation action of these nucleotidases toward the metabolites of clinically used nucleoside analog drugs, including gemcitabine, emtricitabine, tenofovir, and acyclovir. Using in vitro incubations and enzyme kinetics, we demonstrate the involvement of NT5C3 in the dephosphorylation of an important antineoplastic agent, fludarabine. Furthermore, we employed mass spectrometry imaging to visualize peptides corresponding to NT5C3 and other major nucleotidases in the kidney cortex and colonic mucosa.

P4, N=140, Not yet recruiting, Zhongshan Hospital, Fudan University; Zhongshan Hospital, Fudan University

P1, N=11, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2025 --> Oct 2026

P1, N=29, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2025 --> Dec 2027 | Trial primary completion date: Oct 2025 --> Dec 2027

Strategies include: (1) Reprogramming M2 to M1 phenotypes using agonists (TLR, STING, CD40) or inhibitors (STAT3/STAT6); (2) Metabolic modulation (targeting glycolysis, fatty acid oxidation, glutaminolysis); (3) Blocking recruitment axes (CCL2/CCR2, CSF-1/CSF-1R, CXCL12/CXCR4); (4) Depleting M2-TAMs (e.g., trabectedin, CAR-T cells, M2pep-drugs); (5) Enhancing phagocytosis (anti-SIRPα/CD47, anti-SIGLEC)...However, the complexity of the glioma microenvironment and blood-brain barrier necessitate combination strategies for clinical translation. Further research is needed to optimize specificity and overcome challenges like compensatory pathways and drug delivery.