bemcentinib (BGB324)

In this study, we targeted PD-L1 using an siRNA and AXL using a blocker (R428) in OVACAR-3 and CaSki cells, ovarian and cervical cancer cell lines, respectively, in the following groups: Scramble-siRNA, PD-L1-siRNA, Scramble-siRNA in conjunction with R428, PD-L1-siRNA in conjunction with R428, R428 monotherapy and untreated controls. Cell viability was assessed by MTT assay after 48 hours of treatment, and cisplatin sensitization was evaluated in resistant OVACAR-3 cells...The results showed a significant decrease in cell proliferation, suppression of EMT-regulating genes, reduction of stemness in cancer cells, increased apoptosis and disruption of the cell cycle in the studied cell lines. These findings suggest that simultaneous blockade of PD-L1 and AXL could serve as a novel tumor-suppressive strategy, especially for cancer patients resistant to ICBs.

These proteins exhibited high-affinity interactions with zavegepant (a clinically approved CGRP receptor antagonist), omilancor, bemcentinib, conivaptan, and APTO-253...Thus, we suggest a systems-level platform for nominating ligandable PDAC targets and clinically actionable compounds. The framework highlights opportunities for rational drug repurposing and motivates future mechanistic studies at the intersection of proteomics and structure-based screening for targets to PDAC.

P3, N=370, Recruiting, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University | Not yet recruiting --> Recruiting

These results emphasize the pivotal role of AXL in regulating both stemness and hedgehog signaling in HER2-positive breast cancer. The study suggests that targeting both AXL and HER2 could be a promising strategy to overcome trastuzumab resistance and improve treatment outcomes.

P3, N=370, Not yet recruiting, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

AIC1 showed the highest binding affinity (- 10.079 kcal/mol), surpassing clinical-stage bemcentinib (- 8.234 kcal/mol)...This work pioneers LLM-driven in silico design of AXL inhibitors, offering a scalable blueprint for accelerated anticancer drug development. The online version contains supplementary material available at 10.1007/s40203-026-00582-y.

Notably, the AXL inhibitor Bemcentinib effectively suppressed CML-BP progression in both in vivo and in vitro models. Collectively, our findings establish SE-driven SOX4 and SMAD3 as key regulators in CML-BP and identify Bemcentinib as a promising therapeutic strategy.

However, bevacizumab (Bev) shows limited therapeutic effects on NSCLC BrM...Targeting CD146 by imaprelimab or AXL by bemcentinib exhibits more effective anti-angiogenic effects than Bev for BrM in vivo. These findings provide novel anti-vascular strategies for BrM. CD146+ BrM-CSCs promotes high vascularization of lung cancer brain metastases through dual enhancement of VEGF/VEFGR, which suggests that targeting CD146 is a novel anti-vascular strategy for BrM.

TAM family kinase inhibitors significantly reduce the proliferation and colony formation of K562-S and K562-R cells by inducing apoptosis, interfering with Wnt/β catenin pathway, and upregulating cell cycle inhibitors.

Although these targeted therapies show potential to overcome resistance and improve patient outcomes, challenges remain due to the complex regulation of EMP. Future directions focus on refining combination strategies and advancing personalized approaches to enhance efficacy across multiple cancer types.

Furthermore, molecular dynamics simulation over 200 ns revealed stable protein-ligand complexes with some minor conformational fluctuations. This study suggests that, after further experimentation, modulating AXL with natural compounds holds promise for combating human malignancies, potentially overcoming limitations of existing synthetic inhibitors such as R428.

Combination therapy using either lenvatinib or sorafenib and selective CAV1 inhibitors (e.g., siCAV1/miR-7), or AXL/FGFR4 inhibitors (e.g., BGB324/BLU9931) effectively overcame pan-TKI resistance. Our findings highlight a previously unrecognized role for CAV1-driven signalling in sustaining tumour dormancy, a critical and challenging therapeutic barrier underlying recurrence and pan-TKI resistance in HCC. Therapeutically targeting these pathways offer a promising and novel strategy to eliminate dormant tumour cells, thereby overcoming resistance and improving treatment outcomes.