Targeted Therapy with Polymeric Nanoparticles in PBRM1-Mutant Biliary Tract Cancers: Harnessing DNA Damage Repair Mechanisms.

Abstract

Biliary tract cancers (BTCs) are aggressive malignancies with a dismal prognosis that require intensive targeted therapy. Approximately 10% of BTCs have PBRM1 mutations, which impede DNA damage repair pathways and make cancer cells more susceptible to DNA-damaging chemicals. This review focus on development of poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles targeting delivery system to selectively deliver chemotherapy into PBRM1-deficient BTC cells. These nanoparticles improve therapy efficacy by increasing medication targeting and retention at tumour locations. In preclinical studies, pharmacokinetic profile of this nanoparticle was encouraging and supported its ability to achieve extended circulation time with high drug accumulation in tumor. The review also highlights potential of Pou3F3:I54N to expedite bioassays for patient selection in BTC targeted therapies.