Biogenic silica accumulation in picoeukaryotes: Novel players in the marine silica cycle.

It is well known that the biological control of oceanic silica cycling is dominated by diatoms, with sponges and radiolarians playing additional roles. Recent studies have revealed that some smaller marine organisms (e.g. the picocyanobacterium Synechococcus) also take up silicic acid (dissolved silica, dSi) and accumulate silica, despite not exhibiting silicon dependent cellular structures. Here, we show biogenic silica (bSi) accumulation in five strains of picoeukaryotes (<2-3 µm), including three novel isolates from the Baltic Sea, and two marine species (Ostreococcus tauri and Micromonas commoda), in cultures grown with added dSi (100 µM). Average bSi accumulation in these novel biosilicifiers was between 30 and 92 amol Si cell-1 . Growth rate and cell size of the picoeukaryotes were not affected by dSi addition. Still, the purpose of bSi accumulation in these smaller eukaryotic organisms lacking silicon dependent structures remains unclear. In line with the increasing recognition of picoeukaryotes in biogeochemical cycling, our findings suggest that they can also play a significant role in silica cycling.

Patient derived organoids to model rare prostate cancer phenotypes.

A major hurdle in the study of rare tumors is a lack of existing preclinical models. Neuroendocrine prostate cancer is an uncommon and aggressive histologic variant of prostate cancer that may arise de novo or as a mechanism of treatment resistance in patients with pre-existing castration-resistant prostate cancer. There are few available models to study neuroendocrine prostate cancer. Here, we report the generation and characterization of tumor organoids derived from needle biopsies of metastatic lesions from four patients. We demonstrate genomic, transcriptomic, and epigenomic concordance between organoids and their corresponding patient tumors. We utilize these organoids to understand the biologic role of the epigenetic modifier EZH2 in driving molecular programs associated with neuroendocrine prostate cancer progression. High-throughput organoid drug screening nominated single agents and drug combinations suggesting repurposing opportunities. This proof of principle study represents a strategy for the study of rare cancer phenotypes.

Personalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine.

Precision medicine is an approach that takes into account the influence of individuals' genes, environment, and lifestyle exposures to tailor interventions. Here, we describe the development of a robust precision cancer care platform that integrates whole-exome sequencing with a living biobank that enables high-throughput drug screens on patient-derived tumor organoids. To date, 56 tumor-derived organoid cultures and 19 patient-derived xenograft (PDX) models have been established from the 769 patients enrolled in an Institutional Review Board-approved clinical trial. Because genomics alone was insufficient to identify therapeutic options for the majority of patients with advanced disease, we used high-throughput drug screening to discover effective treatment strategies. Analysis of tumor-derived cells from four cases, two uterine malignancies and two colon cancers, identified effective drugs and drug combinations that were subsequently validated using 3-D cultures and PDX models. This platform thereby promotes the discovery of novel therapeutic approaches that can be assessed in clinical trials and provides personalized therapeutic options for individual patients where standard clinical options have been exhausted.Significance: Integration of genomic data with drug screening from personalized in vitro and in vivo cancer models guides precision cancer care and fuels next-generation research. Cancer Discov; 7(5); 462-77. ©2017 AACR.See related commentary by Picco and Garnett, p. 456This article is highlighted in the In This Issue feature, p. 443.