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.

P3, N=60, Active, not recruiting, University of California, San Francisco | Recruiting --> Active, not recruiting

A diagnosis of sarcoid dactylitis was made and treatment commenced with a reducing course of prednisolone 40 mg daily, along with hydroxychloroquine 200 mg twice daily...The radiological findings can therefore aid diagnosis. Our case highlights the rare initial presentation of dactylitis as a manifestation of paraneoplastic sarcoid.

P3, N=210, Recruiting, National Taiwan University Hospital

Furthermore, inhibiting the late stage of autophagy with hydroxychloroquine (HCQ) decreased cell viability, while early-stage autophagy inhibition using 3-Methyladenine (3-MA) had no significant effect. These results highlight the critical role of Nrf2 in controlling foam cell development, senescence, and autophagic processes, giving valuable insights into potential therapeutic targets for atherosclerosis.

Chloroquine (CQ) and hydroxychloroquine (HCQ) have shown potential owing to their roles in autophagy modulation and immune regulation. Gene expression profiling and flow-cytometry analyses revealed cell-type-specific differences in apoptosis, mitochondrial potential, and DNA damage, suggesting HCQ's selective anti-tumor potential in gingival carcinoma. These findings highlight HCQ as a repurposed adjuvant therapy that modulates autophagy and apoptosis to enhance chemosensitivity in oral cancer.

P4, N=50, Not yet recruiting, Radboud University Medical Center

P3, N=132, Terminated, Mannkind Corporation | N=234 --> 132 | Trial completion date: Dec 2028 --> Nov 2025 | Recruiting --> Terminated | Trial primary completion date: Aug 2026 --> Nov 2025; Futility

These data support a significant role for a type II IFN-associated immune response in SjD pathogenesis, which is targeted by LEF/HCQ. Proteins associated with type II IFN-driven immune responses hold potential to monitor disease activity and predict treatment response.