sirolimus

P2, N=40, Active, not recruiting, The University of Texas Health Science Center at San Antonio | Recruiting --> Active, not recruiting | Trial completion date: Mar 2026 --> Mar 2027

These findings suggest that rapamycin enhances the mechanistic efficacy of cisplatin by specifically targeting and reducing cisplatin-induced stemness (CD133+ CSC population). This study proposes a viable combination therapy for HNSCC involving an mTOR inhibitor and a platinum-based drug to overcome CSC-mediated resistance.

P2, N=12, Not yet recruiting, Huashan Hospital

P1, N=52, Active, not recruiting, City of Hope Medical Center | Suspended --> Active, not recruiting

In tumor necrosis factor-alpha (TNFα)-induced L6 myotubes, SA significantly suppressed inflammatory cytokine expression through inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling and attenuated forkhead box O3a (FoxO3a)-dependent protein degradation, while restoring protein kinase B (Akt)/mechanistic target of rapamycin (mTOR)-dependent anabolic signaling to promote myogenic differentiation and protein synthesis...Furthermore, molecular docking analysis revealed that SA interacts with the activation pocket of phosphoinositide 3-kinase (PI3K), providing structural insight into the mechanism of anabolic signaling reactivation. Collectively, these findings demonstrate that SA mitigates immobilization-induced skeletal muscle atrophy by suppressing NF-κB-mediated inflammatory signaling and restoring muscle protein turnover through reactivation of the PI3K/Akt/mTOR signaling pathway, highlighting its potential as a functional compound for preserving skeletal muscle health under immobilization conditions.

We detail a two-step mechanism where mTORC1 first 'primes' the enzyme by relieving internal constraints, allowing mTORC2 to complete the activation process. By reconciling these different models and addressing long-standing questions about drug sensitivity, this review establishes a modern framework for S6K1 biology and identifies new opportunities for precise therapeutic intervention.

Several signaling pathways are crucial in CAF development, including fibroblast activation protein (FAP), phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), Janus kinase/signal transducers and activators of transcription (JAK/STAT), nuclear factor κB (NF‑κB), transforming growth factor β (TGF‑β), ferroptosis, apoptosis and autophagy pathways...The present review summarized current studies on small molecule compounds that inhibit CAF progression, encompassing inhibitors of the PI3K/AKT/mTOR, JAK/STAT, TGF‑β and NF‑κB pathways, as well as activators of the FAP, ferroptosis, apoptosis and autophagy pathways. These small molecule compounds underscore the significance of CAFs in tumor progression and suggest novel strategies for cancer treatment by targeting CAFs in clinical settings.

P2, N=330, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Oct 2026 --> Jun 2027

In conclusion, our findings demonstrate that trapping cells in a state of high autophagic flux through simultaneous induction and late stage inhibition, is a potent strategy to trigger non-apoptotic cell death in leukemia. This approach represents a promising therapeutic strategy to overcome apoptosis-resistant leukemia.

Upon confirming KHE diagnosis, we initiated a combined sirolimus and prednisone treatment. In this report, we also discuss the clinical manifestations, imaging features, histopathological characteristics, and treatment options for this KHE subtype and review relevant literature. This case highlights the diagnostic features and therapeutic considerations of superficial KHE without KMP, emphasizing the importance of multidisciplinary evaluation.

Mechanistically, UCK2 interacted with the small GTPase Ras homolog enriched in brain (RHEB) and regulated the mechanistic target of rapamycin (mTOR) signaling pathway... UCK2 acts as a prognostic indicator and oncogene in LUAD, at least partly via the RHEB/mTOR axis. Targeting UCK2 may represent a promising therapeutic approach for LUAD.

Collectively, our study delineates a novel non-canonical WNT2B-WASH complex-ATG9A regulatory axis through which WNT2B impairs endosomal trafficking and disrupts autophagy, ultimately amplifying inflammation and fibrosis. This study suggests that WNT2B may serve as a promising therapeutic target for CD and autophagy-associated fibrotic disorders.Abbreviations: 3-MA: 3-methyladenine; AAV: adeno-associated virus; ACTA2: actin alpha 2, smooth muscle; ARPC2: actin related protein 2/3 complex subunit 2; ATG: autophagy related; CCN3: cellular communication network factor 3; CD: Crohn disease; CK666: 2-fluoro-N-[2-(2-methyl-1H-indol-3-yl)ethyl]benzamide; COL1A1: collagen type I alpha 1 chain; Co-IP: co-immunoprecipitation; CTNNB1: catenin beta 1; DBcAMP: dibutyryl cyclic adenosine monophosphate; DPT: dermatopontin; EEA1: early endosome antigen 1; EGFR: epidermal growth factor receptor; ELISA: enzyme-linked immunosorbent assay; ER: endoplasmic reticulum; ESCRT: endosomal sorting complexes required for transport; EV: extracellular vesicle; FRAP: fluorescence recovery after photobleaching; FL: full length; FZD: frizzled class receptor; GST: glutathione S-transferase; HIF: human intestinal fibroblast; HMGB1: high mobility group box 1; IKBKB: inhibitor of nuclear factor kappa B kinase subunit beta; IL6: interleukin 6; LDELS: LC3-dependent EV loading and secretion; LPS: lipopolysaccharide; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MD: middle domain; MEFs: mouse embryonic fibroblasts; MTOR: mechanistic target of rapamycin kinase; MVB: multivesicular body; NFKB: nuclear factor kappa B; NFKBIA: NFKB inhibitor alpha; PDCD6IP: programmed cell death 6 interacting protein; PLA: proximity ligation assay; RELA/p65: RELA proto-oncogene, NF-kB subunit; SAFB: scaffold attachment factor B; SES-CD: Simple Endoscopic Score for Crohn disease; SIM: super-resolution structured illumination microscopy; SMAD3: SMAD family member 3; SQSTM1/p62: sequestosome 1; SRD: spectrin repeat domain; TEM: transmission electron microscopy; TFRC: transferrin receptor; TGFB1: transforming growth factor beta 1; TGOLN2: trans-golgi network protein 2; TNBS: 2,4,6-trinitrobenzenesulfonic acid; TNF: tumor necrosis factor; VCA: Verprolin homology, Central and Acidic; WASHC: WASH complex subunit; WLS: Wnt ligand secretion mediator; WCL: whole cell lysates; WNT: Wnt family member; WT, wild type.