hydroxychloroquine

P=N/A, N=112, Not yet recruiting, Nanfang Hospital, Southern Medical University

Although inhibition of autophagy with hydroxychloroquine and related lysosomal inhibitors has provided proof of concept, their limited specificity has motivated the development of more selective approaches, such as Unc-51-like autophagy activating kinase 1 (ULK1) inhibitors and selective autophagy receptor-directed strategies. Emerging combination regimens that integrate autophagy blockade with KRAS/extracellular signal-regulated kinase (ERK) pathway inhibition, metabolic stress, or immune checkpoint blockade may help overcome chemoresistance and enhance anti-tumor immunity. Together, these advances underscore the therapeutic promise of targeting metabolic plasticity and autophagy in PDAC and lay the groundwork for rational next-generation combination strategies.

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

P2, N=155, Active, not recruiting, University Health Network, Toronto | Trial primary completion date: Apr 2026 --> Dec 2026

Abbreviations: AAV: adeno-associated virus; ACTB/β-actin: actin, beta; AIF1/IBA1: allograft inflammatory factor 1; BAF: bafilomycin A1; BNIP3: BCL2/adenovirus E1B interacting protein 3; CCI: controlled cortical impact; COX8: cytochrome c oxidase subunit 8; CUT&Tag: cleavage under targets and tagmentation; DAPI: 4,'6-diamidino-2-phenylindole; DEGs: differentially expressed genes; eGFP: enhanced green fluorescent protein; EGR1: early growth response 1; GFAP: glial fibrillary acidic protein; GO: gene ontology; GSEA: gene set enrichment analysis; HCQ: hydroxychloroquine; HIF1A/HIF-1α: hypoxia inducible factor 1, alpha subunit; IGV: integrative genomics viewer; KEGG: Kyoto encyclopedia of genes and genomes; KO: knockout; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; Lv: lentivirus; MAP2: microtubule-associated protein 2; mCherry: monomeric cherry fluorescent protein; mRFP: monomeric red fluorescent protein; MTOR: mechanistic target of rapamycin kinase; MUT: mutant; MWM: Morris water maze; NAB1: Ngfi-A binding protein 1; NAB2: Ngfi-A binding protein 2; RBFOX3/NeuN: RNA binding protein, fox-1 homolog (C. elegans) 3; OGD: oxygen-glucose deprivation; OLIG2: oligodendrocyte transcription factor 2; PBS: phosphate-buffered saline; PECAM1/CD31: platelet/endothelial cell adhesion molecule 1; PFA: paraformaldehyde; PPI: protein-protein interaction; Puro: puromycin; ROI: region of interest; ROS: reactive oxygen species; SEM: standard error of the mean; SQSTM1/p62: sequestosome 1; TBI: traumatic brain injury; TOMM20: translocase of outer mitochondrial membrane 20; TSA: tyramide signal amplification; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling; VDAC1: voltage-dependent anion channel 1; WT: wild-type.

Lien exerts anti-HCC effects by promoting autophagy and apoptosis through ROS-mediated inhibition of the PI3K/AKT/mTOR pathway.

P1/2, N=41, Active, not recruiting, Ravi Amaravadi, MD | Recruiting --> Active, not recruiting | N=94 --> 41 | Trial completion date: Jan 2027 --> May 2027 | Trial primary completion date: Jan 2027 --> Jul 2026

P2, N=7, Terminated, Northwestern University | Trial completion date: Jul 2030 --> Apr 2026 | Active, not recruiting --> Terminated | Trial primary completion date: May 2026 --> Oct 2025; The study was closed due to accrual.

Taken together, these findings support itraconazole as a promising candidate for further in vivo and clinical investigation in selected oral cancers, including HNSCC and OSCC. Nevertheless, the definition of clinical treatment schedules will require additional comprehensive pharmacokinetic, toxicological, and clinical studies.

P2, N=7, Active, not recruiting, Northwestern University | Recruiting --> Active, not recruiting | N=43 --> 7 | Trial primary completion date: Jul 2028 --> May 2026

P4, N=10, Not yet recruiting, University of California, San Francisco | Initiation date: Jan 2026 --> Aug 2026

P2, N=334, Recruiting, Centre Hospitalier Universitaire de Saint Etienne | Not yet recruiting --> Recruiting