P2/3, N=210, Recruiting, Hyundai Bioscience Co., Ltd.

To investigate therapeutic options, we utilized patient-derived xenograft (PDX) and tumoroid models established from PDX tumors derived from UDEC patient samples to evaluate everolimus (an mTOR inhibitor) and palbociclib (a CDK4/6 inhibitor), alone and in combination. In a clinical cohort of 29 UDEC patients, higher survivin expression showed a trend toward shorter overall and progression-free survival, supporting its role as a prognostic biomarker. These findings highlight dual PI3K/AKT/mTOR and CDK4/6 inhibition as a promising strategy for UDEC and demonstrate the translational value of PDX and tumoroid models in aggressive gynecologic cancers.

The autophagy agonist rapamycin was used to rescue phenotypic changes...It promotes OSCC progression by enhancing autophagy, potentially through modulating the FOXO pathway. Targeting NSUN3 may represent a novel therapeutic strategy for OSCC.

To further sensitize tumors to ferroptosis, ER-Cu1SAZyme was combined with sirolimus (Srl), an FDA-approved drug, to create the Srl/ER-Cu1SAZyme nanomedicine for coordinated catalytic and metabolic regulation...These results highlight the effectiveness of integrating edge-enriched single-atom catalysis with lipid metabolic modulation to enhance ferroptosis-based tumor therapy. The Srl/ER-Cu1SAZyme nanomedicine offers a safe and highly potent approach for dual catalytic-metabolic regulation in cancer treatment.

Compound 5 demonstrates distinct biological effects compared to torkinib and represents a promising candidate for further development as an mTOR inhibitor targeting both cancer and senescent cells.

The pathogenic defect in LAM occurs due to mutations in the tuberous sclerosis complex (TSC) genes, resulting in failure to suppress the mechanistic target of rapamycin (mTOR) pathway activation, which drives abnormal cell proliferation and lymphangiogenesis...These insights open new avenues for treatment. A better understanding of these pathways will pave the way for more durable and individualised treatments for LAM.

Mechanistic studies demonstrated that ICAld exerts significant adjunctive antitumor effects both in vitro and in vivo in a dose-dependent manner in mouse models; it acts by activating the aryl hydrocarbon receptor (AHR)/cytochrome P450 family 1 subfamily A member 1 (CYP1A1)/reactive oxygen species (ROS) axis, inhibiting the phosphatidylinositol 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) signaling pathway, promoting apoptosis, and synergizing with cyclophosphamide. An aryl hydrocarbon receptor antagonist reversed both the chemosensitizing and intestinal protective effects of L. reuteri HG001 and ICAld. This study elucidates a microbiota-mediated mechanism in DLBCL and supports L. reuteri HG001 as a probiotic adjuvant to enhance therapy while reducing toxicity.

The prognostic model constructed based on ferroptosis-related lncRNAs demonstrates considerable reliability. It not only effectively predicts patient survival but also reflects tumor immune status and drug response characteristics, showing potential as an auxiliary tool for prognosis assessment and personalized treatment in DLBCL.

BTF3 may serve as a promising prognostic biomarker and a potential target for immunotherapeutic intervention across multiple cancer types.

Pharmacologic targeting of NDUFS4 using the niclosamide analog ARVib-7 phenocopied genetic depletion, suppressing mitochondrial respiration and enhancing olaparib efficacy to inhibit the growth of resistant spheroids. These findings identify NDUFS4 as a key mediator of PARPi resistance and a therapeutic vulnerability in advanced prostate cancer. Targeting NDUFS4 disrupts OxPhos and induces ferroptosis, providing a strong rationale for combination strategies with PARPis to overcome drug resistance.

Since RAPTOR is an essential component of mTORC1 and lacks a direct inhibitor, the mTORC1 inhibitor rapamycin was used as a pharmacological surrogate to assess the therapeutic potential of targeting RAPTOR-mediated signaling...CONCLUSIONS This study identifies a novel protein-based prognostic model for HNSCC and demonstrates that RAPTOR promotes tumor progression through mTOR signaling and S100A8/A9-uPA regulation. Targeting RAPTOR-mediated pathways may offer new strategies for precision therapy in HNSCC.

P2, N=340, Recruiting, National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Jun 2029 --> Jun 2030 | Trial primary completion date: Jun 2027 --> Jun 2028