International Consensus Conference for Advanced Breast Cancer, Lisbon 2019: ABC5 Consensus – Assessment by a German Group of Experts

The 5th International Consensus Conference for Advanced Breast Cancer (ABC5) took place on November 14–16, 2019, in Lisbon, Portugal. Its aim is to standardize the treatment of advanced breast cancer based on the available evidence and to ensure that all breast cancer patients worldwide receive adequate treatment and access to new therapies. This year, the conference focused on developments and study results in the treatment of patients with hormone receptor-positive/HER2-negative breast cancer as well as precision medicine. As in previous years, patient advocates from around the world were integrated into the ABC conference and had seats on the ABC consensus panel. In the present paper, a working group of German breast cancer experts comments on the results of the on-site ABC5 consensus votes by ABC panelists regarding their applicability for routine treatment in Germany. These comments take the recommendations of the Breast Committee of the Gynecological Oncology Working Group (Arbeitsgemeinschaft Gynäkologische Onkologie; AGO) into account. The report and assessment presented here pertain to the preliminary results of the ABC5 consensus. The final version of the statements will be published in Annals of Oncology and The Breast

Access to the uncultured microbial life: A functional metagenomic RubisCO screen reveals a novel ribulose-1,5-bisphosphate converting enzyme

Most of Earth's microbial diversity resists cultivation in the laboratory, which makes physiological characterizations hard, if not impossible. Consequently, metabolic activities and possible contributions to global elemental cycles have to be predicted from genomics and environmental characteristics, and many new metabolic enzymes and pathways remain undiscovered. To close this knowledge gap, we are using functional metagenomics to access and elucidate the unknown potential of numerous novel enzyme functions and metabolic pathways. Here, we report on the establishment and successful use of one of our function-based metagenomic screens that allows us to mine and investigate RubisCOs (Ribulose-1,5-bisphosphate carboxylase/oxygenase) from the environment independent of the culturability of the native host. RubisCO is well known as a key enzyme in the biological carbon cycle. This enzyme mediates the fixation of more than 90% of the world's inorganic carbon into biomass by catalyzing the carboxylation of ribulose-1,5-bisphosphate (RuBP), leading to the formation of two molecules 3-phospho-D-glycerate (3-PGA). Screening of 15,000 fosmid clones from deep-sea hydrothermal vents resulted in the recovery of 41 recombinant RubisCO active fosmid clones originating from distinct phyla. Next to identifying various active RubisCOs from uncultured microbes and gaining new insights into RubisCO regulation and activation processes, we found one clone that was particularly striking. This clone converted RuBP not only exceptionally fast (up to 20 mM is converted within a few seconds), but also does not form 3-PGA. Indeed, biochemical characterization and crystallization of the overexpressed novel enzyme confirms that it is a novel RuBP converting phosphatase. This is surprising as substantial RuBP conversion in bacteria has so far only been observed in the context of autotrophic CO2 fixation via RubisCO. Thus, this novel phosphatase has the potential to change our current understanding of RuBP associated metabolism, as it possesses a yet unknown function in a previously unrecognized RuBP pathway