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Histone Deacetylase Inhibitors Research / Cancer, Hypoxia, and Metabolism · Journal article
Cancer Drug Resistance · September 7, 2026
Raises a question worth testing. It does not answer one.
This is a narrative literature review proposing PSMD14, a deubiquitinase, as a translational target in oncology and other diseases based on preclinical characterization of its role in protein stabilization and drug resistance. The review identifies a translational gap between mechanistic insights in cancer cell models and clinical application, and surveys potential PSMD14 inhibitors (thiolutin, Capzimin, O-phenanthroline) and dual-target agents, but does not report new clinical efficacy or comparative effectiveness data.
Journal article. Patients with multiple malignancies (hepatocellular carcinoma, pancreatic cancer, lung cancer) and non-tumor conditions (glucocorticoid-induced osteoporosis, post-cardiac arrest neurological outcomes), based on literature synthesis..
PSMD14 drives therapeutic resistance to multiple agents including cisplatin, oxaliplatin, temozolomide, anlotinib, tamoxifen, and bortezomib by deubiquitinating and stabilizing key effectors. PSMD14 has prognostic value as a biomarker for overall survival and recurrence prediction in hepatocellular carcinoma, pancreatic cancer, and lung cancer. Emerging PSMD14 inhibitors include natural products (thiolutin) and synthetic agents (Capzimin, O-phenanthroline) plus next-generation dual-target inhibitors.
No original clinical trial data, efficacy figures, or safety outcomes reported. Clinical barriers to PSMD14-targeted therapy translation include off-target toxicity, patient stratification, and optimal combination strategy definition.
This review raises questions about PSMD14 inhibition as a precision therapy strategy but does not yet provide evidence sufficient to guide clinical decision-making. Clinicians should regard PSMD14-targeted agents as experimental until clinical trial data become available.
This is a narrative review synthesizing preclinical mechanistic evidence and proposing PSMD14 as a therapeutic target, but it does not report new empirical data, clinical trials, or outcomes in patients.
This review raises questions about PSMD14 inhibition as a precision therapy strategy but does not yet provide evidence sufficient to guide clinical decision-making. Clinicians should regard PSMD14-targeted agents as experimental until clinical trial data become available.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
What is missing. This record has no reported figures. That is a gap in the analysis, not a judgement about the study.
The deubiquitinase PSMD14 (also known as RPN11 or POH1), a critical component of the JAB1/MPN/Mov34 metalloenzyme family, has emerged as a pivotal regulator of protein homeostasis through its deubiquitinating activity. While preclinical studies have extensively characterized PSMD14-mediated stabilization of oncogenic substrates involved in cell cycle progression, programmed cell death, metastasis, metabolic reprogramming, and immune evasion, a translational gap remains between these mechanistic insights and clinical application. This review synthesizes current evidence demonstrating that PSMD14 drives therapeutic resistance across multiple malignancies, including resistance to cisplatin, oxaliplatin, temozolomide, anlotinib, tamoxifen, and bortezomib by deubiquitinating and stabilizing key effectors such as E2F1, ALK2, IMPDH2, estrogen receptor α, and proteasomal components. Furthermore, we highlight the prognostic value of PSMD14 as a biomarker for overall survival and recurrence prediction in hepatocellular carcinoma, pancreatic cancer, lung cancer, and other malignancies, along with its emerging role in non-tumor conditions such as glucocorticoid-induced osteoporosis and post-cardiac arrest neurological outcomes. We critically evaluate the therapeutic landscape of PSMD14 inhibitors, from natural products (thiolutin) and synthetic agents (Capzimin, O-phenanthroline) to next-generation dual-target inhibitors, and discuss the clinical barriers to translation, including off-target toxicity, patient stratification, and optimal combination strategies. By integrating mechanistic discovery with biomarker development and inhibitor optimization, this review aims to lay a foundation for the future development of PSMD14-targeted therapeutic strategies.
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