Plectin-targeted liposomes enhance the therapeutic efficacy of a PARP inhibitor in the treatment of ovarian cancer

Theranostics
Siva Sai Krishna DasaKimberly A Kelly

Abstract

Advances in genomics and proteomics drive precision medicine by providing actionable genetic alterations and molecularly targeted therapies, respectively. While genomic analysis and medicinal chemistry have advanced patient stratification with treatments tailored to the genetic profile of a patient's tumor, proteomic targeting has the potential to enhance the therapeutic index of drugs like poly(ADP-ribose) polymerase (PARP) inhibitors. PARP inhibitors in breast and ovarian cancer patients with BRCA1/2 mutations have shown promise. About 10% of the patients who received Olaparib (PARP inhibitor) showed adverse side effects including neutropenia, thrombocytopenia and in some cases resulted in myelodysplastic syndrome, indicating that off-target effects were substantial in these patients. Through proteomic analysis, our lab previously identified plectin, a cytolinker protein that mislocalized onto the cell surface during malignant transformation of healthy ovarian tissue. This cancer specific phenotype allowed us to image pancreatic cancer successfully using plectin targeted peptide (PTP) conjugated to nanoparticles or displayed on capsid protein of adeno-associated virus (AAV) particles. Objective: The goal of this study was to ...Continue Reading

Citations

Dec 13, 2019·Journal of Receptor and Signal Transduction Research·Yunpeng TianHaoming Song
Dec 21, 2019·Journal of Receptor and Signal Transduction Research·Yang YangZhiyun Wang
Jan 29, 2020·Journal of Receptor and Signal Transduction Research·Peng LiQiuyun Tu
Jul 17, 2020·Disease Markers·Xiaojing YangJie Fu
Sep 10, 2020·International Journal of Peptide Research and Therapeutics·Chunyan LiHong Yang
Nov 23, 2019·Journal of Receptor and Signal Transduction Research·Guanqun Ma, Yingwu Liu
Aug 25, 2020·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Rachael M CristStephan T Stern
Jan 15, 2019·European Journal of Medicinal Chemistry·Mingyuan LiHervé Galons
Oct 19, 2020·International Journal of Pharmaceutics·Yuan LiHuile Gao
Dec 30, 2021·Cellular and Molecular Life Sciences : CMLS·Abiola Abdulrahman AyanlajaDianshuai Gao

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Methods Mentioned

BETA
biosensor
light scattering
flow cytometry
biolayer interferometry
size exclusion chromatography

Software Mentioned

ImageQuant
imageJ
prism
MATLAB
FMT

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