In parallel, suppression of anabolic signaling, particularly impairment of the insulin-like growth factor-1/Akt/mechanistic target of rapamycin complex 1 (mTORC1) pathway, has been reported, indicating a shift in muscle protein turnover toward a catabolic state. By distinguishing drug-induced muscle toxicity from cancer cachexia and other wasting conditions, we propose that skeletal muscle should be recognized as a clinically relevant but underestimated target organ of cisplatin toxicity. Improved understanding of these processes may support the development of strategies to preserve muscle mass and function during cancer chemotherapy.

P2, N=30, Not yet recruiting, AFT Pharmaceuticals, Ltd. | Initiation date: Apr 2026 --> Aug 2026

P3, N=236, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Mar 2027 --> Mar 2026

The addition of everolimus, a mammalian target of rapamycin inhibitor, to octreotide marginally improves the 6-month progression-free survival (PFS) rate...We present the first case of a refractory meningioma patient treated with combination PRRT and octreotide in a 66-year-old male who received 177Lu-DOTATATE 7.4 GBq (200 mCi) and intramuscular long-acting octreotide 40 mg every 8 weeks for four cycles followed by a single cycle of octreotide 40 mg monotherapy...A 7-week post-treatment MRI brain demonstrated stable disease with 11.5% reduction per RANO-Meningioma and a 2.6% reduction per RECIST 1.1 criteria. Combined PRRT and octreotide represents a promising therapeutic strategy for patients with refractory meningioma.

Emerging evidence also implicates LHX2 in metabolic-epigenetic circuits, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) and Wingless/Int-1 (Wnt)/β-catenin axes, as well as microRNA (miRNA) regulation. We also discuss therapeutic strategies targeting LHX2, including molecular engineering to overcome species barriers, and outline key knowledge gaps. A comprehensive understanding of LHX2-regulated networks holds promise for advancing regenerative medicine and enabling precision interventions in developmental disorders.

P2, N=53, Active, not recruiting, Abramson Cancer Center at Penn Medicine | Trial completion date: Jan 2026 --> Jan 2027

Drug sensitivity prediction showed lower predicted half-maximal inhibitory concentration (IC50) values for selected agents, including AZD8055, in the high-risk subgroup, suggesting a potential association with pharmacogenomic drug-response patterns...RT-qPCR confirmed downregulation of ABCG4 and GPX3 and upregulation of SERPINE1 in GC cell lines. These findings identified prognostic features associated with uric acid metabolism in gastric cancer and suggest that ABCG4, SERPINE1, and GPX3 may be involved in metabolic dysregulation, matrix remodeling, and predicted pharmacogenomics response patterns.

Drug response prediction suggested reduced sensitivity to platinum chemotherapy and epidermal growth factor receptor (EGFR) inhibitors but increased sensitivity to phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) inhibitors...The Glyco. marker system provides a potential framework for prognostic assessment and precision oncology strategies in LUAD.

Chronic hyperinsulinemia can activate insulin-like growth factor-1-dependent pathways, including phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin and mitogen-activated protein kinase signaling, promoting cellular proliferation while limiting apoptosis...Pharmacological therapies, including glucagon-like peptide-1 receptor agonists and dual incretin agents, offer additional metabolic benefits, although their long-term impact on cancer risk is still unclear. Therefore, IR is best understood not as an isolated risk factor, but as a systemic metabolic risk state that may influence cancer development, with implications for prevention and early risk stratification.

Pathway enrichment analysis suggested that the potential target genes of hsa-miR-103a-3p were mainly enriched in AMP-activated protein kinase, mechanistic target of rapamycin, tumor necrosis factor, insulin signaling, and cellular senescence pathways...These findings suggest that adult S. japonicum worms may alter the miRNA expression profile of hepatic stellate cells, and that hsa-miR-103a-3p may be associated with fibrogenic responses and may have potential relevance to hepatocellular carcinoma-related processes. However, this inference is based on correlative TCGA data and does not imply a causal role in schistosomiasis-associated hepatocarcinogenesis.

The functional roles of MALAT1 siRNA, miR-204-5p mimics/antagomirs, rapamycin, and 3-methyladenine (3-MA) on LC3B expression and autophagic activation were assessed by Western blot and immunofluorescence confocal microscopy for LC3B puncta formation... In HCF-aa subjected to RES, MALAT1 functions intracellularly as a competing endogenous RNA to putatively sequester miR-204-5p, thereby de-repressing LC3B expression and promoting autophagic activation. Concurrent exosomal secretion of MALAT1 may additionally serve as a paracrine signal to neighboring cells, though this requires future conditioned-media transfer experiments to confirm.

While mTOR inhibitor sirolimus, the only FDA approved drug for this disease, stabilizes lung function in most LAM patients, the drug does not eliminate LAM cells, underscoring a critical gap in our understanding of the tumor microenvironment and cellular heterogeneity that drive disease progression...Findings were validated through multimodal imaging technologies. Present work advances the field by providing the first high-resolution blueprint of the LAM niche microenvironment, revealing novel cell states and crosstalk that identify promising therapeutic targets.