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Nanoparticle-based targeted cancer strategies for non-invasive prostate cancer intervention.

ABSTRACT: Prostate cancer is screened by testing circulating levels of the prostate-specific antigen (PSA) biomarker, monitoring changes over time, or a digital rectal exam. Abnormal results often lead to prostate biopsy. Prostate cancer positive patients are stratified into very low-risk, low-risk, intermediate-risk, and high-risk, based on clinical classification parameters, to assess therapy options. However, there remains a gap in our knowledge and a compelling need for improved risk stratification to inform clinical decisions and reduce both over-diagnosis and over-treatment. Further, current strategies for clinical intervention do not distinguish clinically aggressive prostate cancer from indolent disease. This mini-review takes advantage of a large number of functionally characterized microRNAs (miRNA), epigenetic regulators of prostate cancer, that define prostate cancer cell activity, tumor stage, and circulate as biomarkers to monitor disease progression. Nanoparticles provide an effective platform for targeted delivery of miRNA inhibitors or mimics specifically to prostate tumor cells to inhibit cancer progression. Several prostate-specific transmembrane proteins expressed at elevated levels in prostate tumors are under investigation for targeting therapeutic agents to prostate cancer cells. Given that prostate cancer progresses slowly, circulating miRNAs can be monitored to identify tumor progression in indolent disease, allowing identification of miRNAs for nanoparticle intervention before the crucial point of transition to aggressive disease. Here, we describe clinically significant and non-invasive intervention nanoparticle strategies being used in clinical trials for drug and nucleic acid delivery. The advantages of mesoporous silica-based nanoparticles and a number of candidate miRNAs for inhibition of prostate cancer are discussed.

SUBMITTER: Farina NH

PROVIDER: S-EPMC5993634 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Nanoparticle-based targeted cancer strategies for non-invasive prostate cancer intervention.

Farina Nicholas H NH Zingiryan Areg A Vrolijk Michael A MA Perrapato Scott D SD Ades Steven S Stein Gary S GS Lian Jane B JB Landry Christopher C CC

Journal of cellular physiology 20180416 9

Prostate cancer is screened by testing circulating levels of the prostate-specific antigen (PSA) biomarker, monitoring changes over time, or a digital rectal exam. Abnormal results often lead to prostate biopsy. Prostate cancer positive patients are stratified into very low-risk, low-risk, intermediate-risk, and high-risk, based on clinical classification parameters, to assess therapy options. However, there remains a gap in our knowledge and a compelling need for improved risk stratification to ...[more]

PMID: 29663383

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Project description:BackgroundTo evaluate the cost-effectiveness of six diagnostic strategies involving magnetic resonance imaging (MRI) targeted biopsy for diagnosing prostate cancer in initial and repeat biopsy settings from the Singapore healthcare system perspective.MethodsA combined decision tree and Markov model was developed. The starting model population was men with mean age of 65 years referred for a first prostate biopsy due to clinical suspicion of prostate cancer. The six diagnostic strategies were selected for their relevance to local clinical practice. They comprised MRI targeted biopsy following a positive pre-biopsy multiparametric MRI (mpMRI) [Prostate Imaging - Reporting and Data System (PI-RADS) score ≥ 3], systematic biopsy, or saturation biopsy employed in different testing combinations and sequences. Deterministic base case analyses with sensitivity analyses were performed using costs from the healthcare system perspective and quality-adjusted life years (QALY) gained as the outcome measure to yield incremental cost-effectiveness ratios (ICERs).ResultsDeterministic base case analyses showed that Strategy 1 (MRI targeted biopsy alone), Strategy 2 (MRI targeted biopsy ➔ systematic biopsy), and Strategy 4 (MRI targeted biopsy ➔ systematic biopsy ➔ saturation biopsy) were cost-effective options at a willingness-to-pay (WTP) threshold of US$20,000, with ICERs ranging from US$18,975 to US$19,458. Strategies involving MRI targeted biopsy in the repeat biopsy setting were dominated. Sensitivity analyses found the ICERs were affected mostly by changes to the annual discounting rate and prevalence of prostate cancer in men referred for first biopsy, ranging between US$15,755 to US$23,022. Probabilistic sensitivity analyses confirmed Strategy 1 to be the least costly, and Strategies 2 and 4 being the preferred strategies when WTP thresholds were US$20,000 and US$30,000, respectively.Limitations and conclusionsThis study found MRI targeted biopsy to be cost-effective in diagnosing prostate cancer in the biopsy-naïve setting in Singapore.

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Nanoparticle-based targeted cancer strategies for non-invasive prostate cancer intervention.

Publications

Nanoparticle-based targeted cancer strategies for non-invasive prostate cancer intervention.

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