mTOR (Mechanistic target of rapamycin kinase)

Small-molecule ALK inhibitors, including crizotinib, have demonstrated high overall response rates (67%-88%) and complete remission rates (~60%-80%) in relapsed or refractory ALK-positive ALCL, often with rapid clinical responses...In addition, it explores emerging strategies for integrating ALK inhibitors into precision-based management of T-cell lymphomas, including combination approaches with chemotherapy, immunotherapy or antibody-drug conjugates. Collectively, these developments highlight a paradigm shift towards biology-driven, personalized therapy in ALK-positive ALCL.

SIGNIFICANT STATEMENT: This study identifies novel autophagy inducers from high-throughput screening of approved and investigational drugs. The findings highlight key pathways such as mechanistic target of rapamycin inhibition and endoplasmic reticulum stress activation, and demonstrate the ability of these compounds to inhibit angiogenesis, suggesting their potential for repurposing in cancer therapy.

P2, N=86, Recruiting, National Cancer Institute (NCI) | Initiation date: Oct 2026 --> Mar 2026

Mechanistically, IF-induced metabolic stress engages AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), and sirtuin pathways, alters lipid and mitochondrial metabolism, and transiently increases reactive oxygen species (ROS), creating vulnerabilities in prostate tumor cells. Translational evidence suggests potential benefits of integrating IF with standard therapy, but effects may depend on fasting regimen, caloric intake, macronutrient composition, and patient metabolic context, including risk of lean mass loss. This review highlights the metabolic crosstalk between IF and AR signaling and emphasizes the need for future clinical studies incorporating biomarker-guided approaches and body composition monitoring to fully exploit this intersection for improved therapeutic outcomes in prostate cancer.

Specifically, legacy PFAS converged on small COPII coat GTPase SAR1A/SAR1B, consistent with potential mechanistic Target of Rapamycin (mTOR)-linked metabolic reprogramming, whereas the replacement ether PFAS hexafluoropropylene oxide dimer acid (HFPO-DA, commercially known as GenX) showed a distinct targetome highlighted by WD repeat-containing protein 89 (WDR89), suggesting non-nuclear-receptor mechanisms plausibly related to chromatin/complex assembly...Further ontology-based annotation linked the stabilized targets to 279 standardized disease entities, with a predominance of neoplastic outcomes. These findings demonstrate TPP as a new approach methodology for PFAS target discovery, reveal divergent early events for legacy versus replacement chemistries, and provide a proteome-scale framework to prioritize mechanism-based validation and to support evidence-weighted risk assessment of emerging fluorinated alternatives.

The key pathways implicated include mTOR (mechanistic target of rapamycin), NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells), and JAK/STAT (Janus kinase-signal transducer and activator of transcription), which together shape cytokine release, T-cell responsiveness, macrophage function, and natural killer cell-mediated cytotoxicity...Understanding how anesthetic techniques shape perioperative immunity offers an opportunity to refine anesthetic decision-making and develop evidence-based strategies aimed at improving short- and long-term patient outcomes. This article aims to review the effect of anesthetic techniques and medications on the immune response during the perioperative period.

An electronic literature search of Ovid MEDLINE was conducted from database inception to 2025 to identify studies evaluating the role of MTOR in CLD. The review underscores a clear unmet need for well-designed human clinical trials to specifically assess mTOR inhibitors as potential anti-fibrotic therapies.

The review lists over 18 mushroom species (e.g., Ganoderma lucidum, Cordyceps, Phellinus) and 28 bioactive compounds (such as Ganoderic acid DM, Cordycepin, Hispidin) that affect autophagy, demonstrating efficacy against 15 cancer types, including colorectal, lung, breast, and liver cancers...The context-dependent effects of autophagy, along with the limited clinical evidence, present considerable challenges. Future clinical trials must focus on developing standardized extracts and personalized approaches to effectively translate this potential into clinical practice.

Conclusions Lenvatinib showed substantial efficacy in BRAF-mutated PTC, while TERT mutations did not predict poor outcomes. The identification of five genes associated with early treatment failure highlights the potential for genomic biomarkers to guide personalized therapy.

Notably, repurposed drugs exhibit anticancer activity by modulating key pathways, including phosphatidylinositol 3-kinase/Ak strain transforming/mechanistic target of rapamycin, mitogen-activated protein kinase/extracellular signal-regulated kinase, wingless-related integration site/β-catenin signaling, as well as redox homeostasis and DNA response...With cancer causing one in six global deaths and marked by therapeutic resistance and molecular heterogeneity, drug repurposing provides a scalable solution. This approach bridged preclinical insight with clinical application, potentially transforming cancer therapeutics through rational, data-driven innovation.

Elevated levels of IGF-1 expression were observed, while FOXO1 expression was decreased. These findings indicate that early maternal probiotic supplementation improves lymphocyte activity and facilitates the remodeling of the splenic immune system in offspring and thus represents an innovative approach to immune programming during early life.

TC appears to be a heterogeneous disease, exhibiting varying genomic alteration rates. Several somatic and germline aberrations, some of which have been reported in this article for the first time, warrant further investigation for their hinted prognostic value and clinical implications.