EZR links cytoskeletal remodeling to STAT3 signalling to drive metastatic competence and paclitaxel resistance, nominating EZR as a potential therapeutic vulnerability in treatment-refractory breast cancer.

The combination of anti-PD-L1 and paclitaxel (PTX) is a standard-of-care regimen for triple-negative breast cancer (TNBC)...This project aims to construct an albumin-based nanomedicine coloaded with atovaquone (ATO) and PTX for targeted tumor delivery, thereby enhancing the therapeutic efficacy of ICBs...This transformative approach significantly enhances the therapeutic efficacy of combination chemotherapy, leading to potent suppression of primary tumors while concurrently preventing postoperative recurrence and pulmonary metastases. This project has the potential to introduce innovative strategies and methodologies aimed at overcoming the limited efficacy of PTX combined with ICBs in the treatment of TNBC.

P=N/A, N=5, Not yet recruiting, Huashan Hospital, Fudan University; Huashan Hospital, Fudan University

P=N/A, N=40, Not yet recruiting, the Second Affiliated Hospital of Nanchang University; the Second Affiliated Hospital of Nanchang University

P=N/A, N=6, Not yet recruiting, The Affiliated Hospital of Qingdao University; The Affiliated Hospital of Qingdao University

P2, N=77, Not yet recruiting, Zhongshan Hospital Affiliated to Fudan University; Zhongshan Hospital Affiliated to Fudan University

P2, N=30, Not yet recruiting, Zhejiang Cancer Hospital; Zhejiang Cancer Hospital

P1/2, N=120, Recruiting, Shanghai East Hospital; Novatim Immune Therapeutics (Zhejiang) Co., Ltd.

P2, N=40, Recruiting, The Second Affiliated Hospital Zhejiang University School of Medicine; The Second Affiliated Hospital Zhejiang University School of Medicine | Not yet recruiting --> Recruiting

Notably, it effectively inhibited the proliferation of HeLa/Taxol cells (IC50 = 14.47 ± 0.02 μM) while showing low cytotoxicity toward normal liver epithelial THLE-2 cells (IC50 = 26.40 ± 0.04 μM)...SwissADME predictions further supported its potential druggability. Collectively, compound 4k represents a promising lead worthy of further investigation as a potential antitumor agent.

Initial the standard of care (SOC) treatment includes intensive cytoreductive surgery (CRS) and platinum-paclitaxel chemotherapy with/without adding anti-angiogenetic agent and/or following poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) maintenance therapy based on biomarker-guided recommendation, such as BRCA mutation and/or homologous recombination deficiency (HRD significance)...Chemoresistance may be derived from "naïve" (underlying or primary) hereditary or acquired adaption (secondary or induced), which are involved in an increasing ability to self-repairing DNA, dysregulated autophagy process and evasion of apoptosis and alternation in mitochondrial pathways as well as metabolic adaptions, changing signaling pathway for proliferation and survival, and modifying genetic and epigenetic resolution, contributing to sustaining proliferative signaling, resisting cell death, evading growth suppressor, inducing angiogenesis, activating invasion and metastases, deregulating cellular energetics, reaching cellular senescence and stemness, and epigenetic reprogramming of cancer cells. The first part is a brief review for PR-rOC, including mechanisms, and combating strategies but only limited to cytoreductive surgery for treating PR-rOC patients.

Co-administration of Marine Bromophenol Derivative (OSBP63) with paclitaxel (PTX), a conventional anticancer drug, significantly suppressed B-cell lymphoma-2 (BCL-2) expression and protein kinase B (AKT) phosphorylation, thereby demonstrating pronounced anti-tumor activity in a mouse model of breast cancer. These findings suggest that OSBP63 represents a promising non-CDN small-molecule STING agonist candidate, offering a valuable lead for future anticancer therapeutic development.