Rapamycin also reduced hepatosteatosis, total body weight, and a tumorigenic transcriptomic signature associated with hepatocellular carcinoma risk. These findings demonstrate that aging intensifies hepatic sensitivity to dietary metabolic stress and identify rapamycin as a promising therapeutic to counteract age-related liver dysfunction and metabolic dysfunction-associated steatotic liver disease (MASLD) progression.

P3, N=440, Not yet recruiting, Shanghai Jiatan Pharmatech Co., Ltd

The mechanistic target of rapamycin (mTOR) is a central regulator of cell growth and a promising cancer therapeutic target...In the HGC-27 xenograft mouse model, oral administration of T133 exhibited dose-dependent efficacy comparable to clinical-stage inhibitor PF-04691502, while exhibiting significantly reduced hepatotoxicity, nephrotoxicity, and pulmonary toxicity. Moreover, assessments of T133 on cytochrome P450, hERG, and AMES indicate a favorable safety profile. These findings suggest T133 is a promising mTOR inhibitor, warranting further investigation for cancer therapy.

Our findings suggest efficacy of PI3K inhibition + tamoxifen beyond second-line treatment and after prior targeted therapies, including CDK4/6 inhibition in metastatic HR+/HER2- breast cancer although the magnitude of benefit did not outweigh the tolerability of this combination. Exploratory biomarker analysis indicates that tumor fraction determined in ctDNA differentiates patients based on prognosis and may help to optimize patient selection for targeted treatment strategies.

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.