P2, N=50, Completed, Shanghai Children's Hospital | Recruiting --> Completed

The combination of BINI + HCQ demonstrated a challenging toxicity profile and limited clinical activity in patients with chemorefractory metastatic PDAC.

Difluprednate showed the highest pharmacovigilance signal (ROR: 963.67; 95% CI: 316.27-2936.31; n = 4). Notably, CFTR modulators exhibited striking signals: ivacaftor (ROR: 30.75; 95% CI: 18.06-52.37; n = 14), elexacaftor-ivacaftor-tezacaftor (ROR: 15.58; 95% CI: 9.86-24.63; n = 19), and ivacaftor-lumacaftor (ROR: 13.2; 95% CI: 7.9-22.07; n = 15). This study provides a comprehensive large-scale pharmacovigilance profile of drug-induced pediatric cataracts, identifying agents with high-risk pharmacovigilance signals and underscoring the need for proactive ocular monitoring. These findings can inform clinical decision making and prevention strategies and guide future mechanistic research.

CM@pGGH is synthesized by conjugating GA and hydroxychloroquine (HCQ)-an FDA-approved antimalarial and immunomodulator-to polyglutamic acid (PGA) using disulfide and ester linkages, followed by incorporation of a hybrid membrane derived from tumor cell and macrophage...In vivo, CM@pGGH reprograms the tumor immune microenvironment by repolarizing tumor-associated macrophages to a pro-inflammatory M1 phenotype and promoting CD8+ T-cell infiltration, resulting in significant PANoptosis-driven immunogenic cell death (ICD) and sustained antitumor immunity. These findings highlight a dual-prodrug and immune-reprogramming strategy with potential for treating refractory cancers.

P=N/A, N=90, Not yet recruiting, Sohag University

P4, N=30, Not yet recruiting, Walter and Eliza Hall Institute of Medical Research

P2, N=25, Completed, University Hospital, Rouen | Unknown status --> Completed

P1/2, N=31, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> May 2026 | Trial primary completion date: Jan 2026 --> May 2026

During this period, she received escalating immunosuppression with corticosteroids, mycophenolate, and cyclophosphamide...Immunosuppression was de-escalated to hydroxychloroquine alone with no recurrence at 14-month follow-up...Cardiac myxomas produce IL-6 in the majority of patients (frequency >75%), and systemic constitutional signs are observed in a substantial proportion, though not uniformly. This can produce IL-6-mediated inflammation indistinguishable from autoimmune flares.

In addition, we critically appraise clinical attempts to modulate autophagy (e.g., with chloroquine/hydroxychloroquine (CQ/HCQ) or mTOR inhibitors), outlining reasons for mixed outcomes and proposing practical solutions for future trials. Finally, potential targeted therapeutic strategies are discussed, including approaches to inhibit cytoprotective autophagy and strategies to induce autophagy-dependent cell death using novel small-molecule activators. Collectively, the evidence supports a model in which precise, context-aware modulation of autophagy-guided by pharmacodynamic (PD) biomarkers and molecular stratification-will be key to improving outcomes in lung cancer.

P=N/A, N=102, Completed, University Hospital, Toulouse | Recruiting --> Completed | N=50 --> 102

In vivo analyses using subcutaneous and spontaneous murine PDAC models revealed elevated ROS in tumors, which were significantly reduced upon genetic deletion of host MPO or peptidyl arginine deiminase 4, an essential enzyme for NET formation, or after treatment with hydroxychloroquine, a NET inhibitor...Importantly, ROS levels correlated strongly with NET formation in patient samples. These findings reveal a bidirectional relationship between ROS and NETs and highlight the potential utility of L-012- and [18F]4FN-based PET imaging for monitoring NET-associated inflammation in PDAC in vivo.