A Systematic Review of Cost-Effectiveness Analyses for Hepatocellular Carcinoma Treatment.

BACKGROUND: Hepatocellular carcinoma (HCC) is associated with significant financial burden for patients and payers. The objective of this study was to review economic models to identify, evaluate, and compare cost-effectiveness estimates for HCC treatments. METHODS: A systematic search of the PubMed, Embase, and Cochrane Library databases to identify economic evaluations was performed and studies that modeled treatments for HCC reporting costs and cost effectiveness were included. Risk of bias was assessed qualitatively, considering costing approach, reported study perspective, and funding received. Intervention costs were adjusted to 2021 US dollars for comparison. For studies reporting quality-adjusted life-years (QALYs), we conducted analyses stratified by comparison type to assess cost effectiveness at the time of the analysis. RESULTS: A total of 27 studies were included. Non-curative versus non-curative therapy comparisons were used in 20 (74.1%) studies, curative versus curative comparisons were used in 5 (18.5%) studies, and curative versus non-curative comparisons were used in 2 (7.4%) studies. Therapy effectiveness was estimated using a QALY measure in 20 (74.1%) studies, while 7 (25.9%) studies only assessed life-years gained (LYG). A health sector perspective was used in 26 (96.3%) of the evaluations, with only 1 study including costs beyond this perspective. Median intervention cost was $53,954 (range $4550-$4,760,835), with a median incremental cost of $6546 (range - $72,441 to $1,279,764). In cost-utility analyses, 11 (55%) studies found the intervention cost effective using a $100,000/QALY threshold at the time of the study, with an incremental cost-effectiveness ratio (ICER) ranging from - $1,176,091 to $1,152,440 when inflated to 2021 US dollars. CONCLUSION: The majority of HCC treatments were found to be cost effective, but with significant variation and with few studies considering indirect costs. Standards for value assessment for HCC treatments may help improve consistency and comparability.

Racial and Ethnic Differences in Drug Disposition and Response: Review of New Molecular Entities Approved Between 2014 and 2019.

Race and ethnicity can contribute to differences in drug exposure and/or response. Here, we report that about 10% of the new molecular entities (NMEs) approved between 2014 and 2019 by the US Food and Drug Administration's Center for Drug Evaluation and Research showed differences in exposure and/or response based on race/ethnicity or pharmacogenetic factors known to vary in frequency across global populations. Fewer NMEs (10%) reported differences in the labeling in 2014 to 2019 when compared to about 21% of NMEs approved between 2008 and 2013 that had differences in pharmacokinetics, safety, response, and/or pharmacogenetics. Understanding the underlying mechanisms that lead to such differences and adequate enrollment of racial and ethnic subgroups is essential to obtain sufficient information on exposure and response. Though drug development is global, when heterogeneous populations are not adequately enrolled, the risk-benefit assessments can remain incomplete for certain subgroups. Consequently, this can result in regional differences in drug approval, population-specific prescribing recommendations, or need for additional postmarketing studies to address concerns related to exposure, response, or lack of representation that lead to gaps in information.

SOX4 regulates invasion of bladder cancer cells via repression of WNT5a.

Sry­Related HMG­BOX­4 (SOX4) is a developmental transcription factor that is overexpressed in as many as 23% of bladder cancer patients; however, the role of SOX4 in bladder cancer tumorigenesis is not yet well understood. Given the many roles of SOX4 in embryonic development and the context­dependent regulation of gene expression, in this study, we sought to determine the role of SOX4 in bladder cancer and to identify SOX4­regulated genes that may contribute to tumorigenesis. For this purpose, we employed a CRISPR interference (CRISPRi) method to transcriptionally repress SOX4 expression in T24 bladder cancer cell lines, 'rescued' these cell lines with the lentiviral­mediated expression of SOX4, and performed whole genome expression profiling. The cells in which SOX4 was knocked down (T24­SOX4­KD) exhibited decreased invasive capabilities, but no changes in migration or proliferation, whereas rescue experiments with SOX4 lentiviral vector restored the invasive phenotype. Gene expression profiling revealed 173 high confidence SOX4­regulated genes, including WNT5a as a potential target of repression by SOX4. Treatment of the T24­SOX4­KD cells with a WNT5a antagonist restored the invasive phenotype observed in the T24­scramble control cells and the SOX4 lentiviral­rescued cells. High WNT5a expression was associated with a decreased invasion and WNT5a expression inversely correlated with SOX4 expression, suggesting that SOX4 can negatively regulate WNT5a levels either directly or indirectly and that WNT5a likely plays a protective role against invasion in bladder cancer cells.

Bioresponsive polymer coated drug nanorods for breast cancer treatment.

Ineffective drug release at the target site is among the top challenges for cancer treatment. This reflects the facts that interaction with the physiological condition can denature active ingredients of drugs, and low delivery to the disease microenvironment leads to poor therapeutic outcomes. We hypothesize that depositing a thin layer of bioresponsive polymer on the surface of drug nanoparticles would not only protect drugs from degradation but also allow the release of drugs at the target site. Here, we report a one-step process to prepare bioresponsive polymer coated drug nanorods (NRs) from liquid precursors using the solvent diffusion method. A thin layer (10.3 ± 1.4 nm) of poly(ε-caprolactone) (PCL) polymer coating was deposited on the surface of camptothecin (CPT) anti-cancer drug NRs. The mean size of PCL-coated CPT NRs was 500.9 ± 91.3 nm length × 122.7 ± 10.1 nm width. The PCL polymer coating was biodegradable at acidic pH 6 as determined by Fourier transform infrared spectroscopy. CPT drugs were released up to 51.5% when PCL coating dissolved into non-toxic carboxyl and hydroxyl groups. Trastuzumab (TTZ), a humanized IgG monoclonal antibody, was conjugated to the NR surface for breast cancer cell targeting. Combination treatments using CPT and TTZ decreased the HER-2 positive BT-474 breast cancer cell growth by 66.9 ± 5.3% in vitro. These results suggest effective combination treatments of breast cancer cells using bioresponsive polymer coated drug delivery.