Both compounds displayed potent antiproliferative activity across multiple cancer cell lines, with higher potency than NEO2734, paclitaxel (PTX), and ARV-771. In a PC-3 xenograft mouse model, compound 29c achieved dose-dependent tumor growth inhibition (TGI) of up to 81.5% at a low dose of 0.2 mg/kg, administered every other day, significantly surpassing the efficacy of NEO2734 and PTX at higher doses. Together, 29c, a highly efficient CBP/p300 and BRD4 dual-target degrader, demonstrates significant therapeutic potential in prostate cancer and warrants further development.
An ALC ≥ 1000/μL at ERI completion was associated with an improved post-ERI OS (OS2). It is suggested that not only the factors at the initiation of ERI, but also the immunological status at the end of ERI, may have prognostic value after ERI.
P2, N=50, Not yet recruiting, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University; Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
We separately described outcomes and treatment patterns of patients with resectable and unresectable RPS. Our findings suggest that eribulin should be considered a treatment option for unresectable RPS in clinical practice.
Moreover, BB-1701, a novel HER2-ADC containing eribulin as a payload, to which N87 AR cells are sensitive, exhibited antitumor effects in N87 AR cells in vitro and in vivo. These findings indicate that ABC transporter-mediated drug efflux is an important mechanism underlying T-DXd resistance in HER2-positive gastric and lung cancer models. Furthermore, our study suggests that both targeting drug efflux pathways and utilizing alternative payloads may be effective strategies for overcoming T-DXd resistance in HER2-positive gastric and lung cancers.
25 days ago
Journal
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HER-2 (Human epidermal growth factor receptor 2) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • ABCG2 (ATP Binding Cassette Subfamily G Member 2)
Compared to CCS1477, it shows comparable in vivo efficacy in the OPM-2 xenograft model and demonstrates more potent antitumor activity in the 22RV1 xenograft model, with tumor growth inhibition values of 56.2% and 72.8%, respectively. Overall, CZL-077 is a promising candidate for the treatment of human cancer as a p300/CBP BRD inhibitor.