P3, N=30, Recruiting, Ain Shams University

P=N/A, N=370, Completed, The First Affiliated Hospital of the Air Force Medical University; The First Affiliated Hospital of the Air Force Medical University

P4, N=221, Not yet recruiting, Shanghai General Hospital; Shanghai General Hospital

Targeting mTOR signaling contributes to the regulation of Galectin-1 immune checkpoint activity in KMT2Ar-ALL. Inhibition of mTOR may represent a potential therapeutic strategy to overcome immune evasion in this leukemia subtype.

EGF/EGFR expression is associated with immunosuppressive microenvironments and adverse outcomes in HGG. Radiomics may provide a non-invasive approach for estimating EGFR expression, although model performance requires external validation and EGFR-ADCs showed partial inhibitory activity within the tested range, though potency remains to be defined.These findings suggest a framework into radiogenomic stratification and targeted therapy in GBM.

Canonical NF-κB signaling is mechanistically related to UM cell survival, proliferation, and migration, as shown by pharmacologic inhibition like BAY11-7082, and niclosamide and genetic modulation like microRNA-9. NF-κB signaling, particularly the canonical branch, is required for UM malignancy, while noncanonical signaling is linked with high-risk features. Branch-specific genetic manipulations and clinically relevant models should be employed in future research to maximize therapeutic strategies.

P4, N=336, Enrolling by invitation, Baylor Research Institute | Trial completion date: Jun 2024 --> Mar 2027 | Trial primary completion date: Jun 2024 --> Mar 2027 | Active, not recruiting --> Enrolling by invitation

The success of post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis has driven efforts to optimize partner therapies that balance GVHD and relapse prevention. We report phase I dose-finding results of PTCy, sirolimus (SIR), and VIC-1911, a selective oral Aurora kinase A (AURKA) inhibitor, following myeloablative allogeneic hematopoietic cell transplantation (alloHCT)...Clinical outcomes included no grade III-IV acute GVHD through day 180 (0%) and low rates of moderate/severe chronic GVHD (6%) and relapse (0%) through 1 year (5/16 received maintenance). The 1-year overall survival for this cohort was 94%.VIC-1911 at 75 mg BID, combined with PTCy and SIR, effectively suppresses AURKA activity, offering promising GVHD and relapse prevention with a favorable safety profile and promising early clinical outcomes.

Reversible resistance to NVP-BEZ235 in ccRCC is driven, at least in part, by an m6A-dependent YTHDF3-SYNM axis. Targeting YTHDF3 or SYNM may provide a rational strategy to overcome PI3K/mTOR inhibitor resistance in ccRCC.

P2, N=17, Terminated, Dana-Farber Cancer Institute | N=47 --> 17 | Active, not recruiting --> Terminated; participants are no longer being examined or receiving intervention

This review consolidates 2023-2025 advances: phase III validation in post-IO/TKI ccRCC (progression-free survival and response-rate gains vs. everolimus), durable first-line activity with cabozantinib, and approval for advanced pheochromocytoma/paraganglioma-including patients ≥ 12 years-extending impact to endocrine and pediatric oncology...Caution is appropriate: overall survival benefit in randomized RCC trials is not yet demonstrated, resistance can emerge, and long-term hematologic and pulmonary effects require surveillance. Together, HIF-2α inhibition establishes a new, clinically actionable axis in GU oncology.

P1/2, N=7, Active, not recruiting, Brigham and Women's Hospital | Recruiting --> Active, not recruiting | N=16 --> 7 | Trial completion date: Dec 2023 --> Jun 2026