PARP inhibitors combined with ionizing radiation induce different effects in melanoma cells and healthy fibroblasts.

BACKGROUND: PARP inhibitors niraparib and talazoparib are FDA approved for special cases of breast cancer. PARP is an interesting repair protein which is frequently affected in cancer cells. We studied the combined action of talazoparib or niraparib with ionizing radiation in melanoma cells and healthy fibroblasts. METHODS: Homologous recombination (HR) status in six different melanoma cell lines and healthy fibroblasts was assessed. Cell cultures were treated with PARP inhibitors talazoparib or niraparib and ionizing radiation (IR). Apoptosis, necrosis and cell cycle distribution was analyzed via flow cytometry. Cell migration was studied by scratch assays. RESULTS: Studied melanoma cell cultures are HR deficient. Studied healthy fibroblasts are HR proficient. Talazoparib and niraparib have congruent effects within the same cell cultures. In all cell cultures, combined treatment increases cell death and G2/M arrest compared to IR. Combined treatment in melanoma cells distinctly increases G2/M arrest. Healthy fibroblasts are less affected by G2/M arrest. Treatment predominantly decelerates or does not modify migration. In two cell cultures migration is enhanced under the inhibitors. CONCLUSIONS: Although the two PARP inhibitors talazoparib and niraparib appear to be suitable for a combination treatment with ionizing radiation in our in vitro studies, a combination treatment cannot generally be recommended. There are clear interindividual differences in the effect of the inhibitors on different melanoma cells. Therefore, the effect on the cancer cells should be studied prior to a combination therapy. Since melanoma cells increase more strongly than fibroblasts in G2/M arrest, the fractional application of combined treatment should be further investigated.

Is useful research data usually shared? An investigation of genome-wide association study summary statistics.

Primary data collected during a research study is often shared and may be reused for new studies. To assess the extent of data sharing in favourable circumstances and whether data sharing checks can be automated, this article investigates summary statistics from primary human genome-wide association studies (GWAS). This type of data is highly suitable for sharing because it is a standard research output, is straightforward to use in future studies (e.g., for secondary analysis), and may be already stored in a standard format for internal sharing within multi-site research projects. Manual checks of 1799 articles from 2010 and 2017 matching a simple PubMed query for molecular epidemiology GWAS were used to identify 314 primary human GWAS papers. Of these, only 13% reported the location of a complete set of GWAS summary data, increasing from 3% in 2010 to 23% in 2017. Whilst information about whether data was shared was typically located clearly within a data availability statement, the exact nature of the shared data was usually unspecified. Thus, data sharing is the exception even in suitable research fields with relatively strong data sharing norms. Moreover, the lack of clear data descriptions within data sharing statements greatly complicates the task of automatically characterising shared data sets.