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Updated: Jun 13, 2025
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Targeted therapy with polymeric nanoparticles in PBRM1-mutant biliary tract cancers: Harnessing DNA damage repair
Hrushikesh Wagh1, Sankha Bhattacharya1
1Department of Pharmaceutics, School of Pharmacy & Technology Management, SVKM'S NMIMS Deemed-to-be University, Shirpur, Maharashtra 425405, India.
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.
Insights
Targeted nanoparticles deliver chemotherapy to biliary tract cancers (BTCs) with PBRM1 mutations, enhancing treatment efficacy. Pou3F3:I54N shows promise for patient selection in these aggressive cancers.
Area of Science:
- Oncology
- Nanotechnology
- Biochemistry
Background:
- Biliary tract cancers (BTCs) are aggressive malignancies with poor prognoses.
- Approximately 10% of BTCs harbor PBRM1 mutations, affecting DNA damage repair and increasing susceptibility to DNA-damaging agents.
Purpose of the Study:
- To review the development of poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles for targeted chemotherapy delivery in PBRM1-deficient BTCs.
- To evaluate the potential of these nanoparticles to improve therapeutic efficacy and patient selection strategies.
Main Methods:
- Development of PLGA-based nanoparticles for selective chemotherapy delivery.
- Preclinical pharmacokinetic studies to assess nanoparticle circulation time and tumor accumulation.
- Exploration of Pou3F3:I54N as a biomarker for patient stratification.
Main Results:
- PLGA nanoparticles demonstrated enhanced drug targeting and retention at tumor sites.
- Preclinical pharmacokinetic profiles indicated extended circulation time and significant drug accumulation in tumors.
- Pou3F3:I54N emerged as a potential biomarker for expediting patient selection.
Conclusions:
- PLGA-based nanoparticles offer a promising strategy for targeted therapy in PBRM1-deficient BTCs.
- These nanoparticles can improve treatment efficacy through enhanced drug delivery and tumor retention.
- Pou3F3:I54N holds potential for optimizing patient selection in BTC targeted therapies.
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