Development of a novel biotherapeutic fusion protein inhibitor for treatment of advanced prostate cancer

Recent advances in targeted therapies have transformed the treatment of several types of cancer. Numerous agents, including small molecule drugs and therapeutic antibodies targeting receptor tyrosine kinases (RTKs) such as EGFR, Her-2 and MET, are currently in clinical trials or have received regulatory approval. These agents are exhibiting impressive clinical responses demonstrating that these RTK pathways are clinically validated drug targets and key drivers of multiple cancers such as breast, lung and colorectal cancers. 

Dr. Ong’s lab has discovered that SEMA3C drives prostate cancer growth and treatment resistance through activation of multiple RTKs via Plexin B1. He has developed a plexin B1 receptor, called Fc fusion protein, that not only is able to inhibit SEMA3C induced activation of EGFR, HER-2 and MET but is also able to inhibit activation of these RTK by their cognate ligands, EGF and HGF.  

Importantly, Dr. Ong has found that PB1SD-Fc potently inhibited progression of LNCaP xenografts post castration in vivo. Currently, effective therapeutics used for treatment of advanced prostate cancer has been limited to AR pathway inhibitors. This fusion protein represents a new multi-RTK inhibitor drugs that may also show activity in treatment of prostate and other cancers driven by EGFR, HER-2 or MET. Thus, Dr. Ong’s findings may have transformative impact on clinical management of prostate and other cancers.