Furthermore, we identify a synergistic antitumor effect between KPT-330 and translation inhibitors, including everolimus and homoharringtonine. Notably, the disruptive impact of KPT-330 on CRC homeostasis extends to other cancer cell lineages, underscoring its broad mechanistic relevance. Collectively, our findings elucidate a novel mechanism through which KPT-330 destabilizes CRC via translational dysregulation and highlight its potential therapeutic utility in combination regimens for DDLPS.

P1, N=94, Not yet recruiting, Zhongda Hospital

P2, N=40, Enrolling by invitation, Guangdong Second Provincial General Hospital

PLD1-inhibitor remodeled phospholipid metabolism, induced ferroptosis and restored QUIZOM response in LSC. Our findings provided the therapeutic and resistant mechanisms of QUIZOM and paved the way for targeted interventions in this AML subtype.

P2, N=61, Not yet recruiting, First People's Hospital of Hangzhou

Moreover, Gossypol exhibited cytotoxic effects on human breast, prostate, and colorectal cancer cell lines, at least partially through downregulating the oncogenic substrates of targeted DUBs such as c-Myc, Mcl-1, MDM2, and Cyclin D1. Collectively, our findings position Gossypol as a promising small-molecule inhibitor targeting DUBs, especially USPs, and provide a rationale for further exploring its therapeutic potential in USP-driven cancers.

P2, N=35, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

KEGG analysis suggested that the toxic mechanisms may be linked to pathways involved in malignancy, the HIF-1 signaling pathway, proteoglycans in cancer, apoptosis, and others. Gossypol demonstrates a significant therapeutic effect against cervical cancer; however, its hepatotoxicity risk, mediated through multiple targets and pathways, requires further investigation.

Our results elucidate quantitative pharmacodynamics of S63845, venetoclax, and cirtuvivint, an agent that is currently being evaluated with venetoclax to treat AML (NCT06484062). Compensatory increases in off-target Bim heterodimer levels in response to either S63845 or venetoclax offer a possible mechanism of clinical drug resistance.

P1, N=6, Completed, University of Illinois at Chicago | Active, not recruiting --> Completed

All patients remained disease-free, with no events of measurable residual disease (MRD) positivity by flow cytometry or molecular analysis documented. These findings preliminarily confirm that venetoclax, cytarabine, and homoharringtonine-based cytoreductive therapy is a safe and effective bridging therapy for allo-HSCT in patients with refractory/relapsed AML and RUNX1::RUNX1T1 fusion gene.

Additionally, HHT inhibits NSCLC migration by modulating epithelial-mesenchymal transition (EMT) signaling. These findings highlight PDIA4 as a critical mediator of HHT efficacy against NSCLC, provide novel insights into PDIA4-associated therapy, and support the translational potential of HHT in NSCLC treatment.