Pharmacogenomic biomarkers in docetaxel treatment of prostate cancer: from discovery to implementation

Prostate cancer is the fifth leading cause of male cancer death worldwide. Although docetaxel chemotherapy has been used for more than fifteen years to treat metastatic castration resistant prostate cancer, the high inter-individual variability of treatment efficacy and toxicity is still not well understood. Since prostate cancer has a high heritability, inherited biomarkers of the genomic signature may be appropriate tools to guide treatment. In this review, we provide an extensive overview and discuss the current state of the art of pharmacogenomic biomarkers modulating docetaxel treatment of prostate cancer. This includes (1) research studies with a focus on germline genomic biomarkers, (2) clinical trials including a range of genetic signatures, and (3) their implementation in treatment guidelines. Based on this work, we suggest that one of the most promising approaches to improve clinical predictive capacity of pharmacogenomic biomarkers in docetaxel treatment of prostate cancer is the use of compound, multigene pharmacogenomic panels defined by specific clinical outcome measures. In conclusion, we discuss the challenges of integrating prostate cancer pharmacogenomic biomarkers into the clinic and the strategies that can be employed to allow a more comprehensive, evidence-based approach to facilitate their clinical integration. Expanding the integration of pharmacogenetic markers in prostate cancer treatment procedures will enhance precision medicine and ultimately improve patient outcomes

Insect herbivores should follow plants escaping their relatives

Neighboring plants within a local community may be separated by many millions of years of evolutionary history, potentially reducing enemy pressure by insect herbivores. However, it is not known how the evolutionary isolation of a plant affects the fitness of an insect herbivore living on such a plant, especially the herbivore's enemy pressure. Here, we suggest that evolutionary isolation of host plants may operate similarly as spatial isolation and reduce the enemy pressure per insect herbivore. We investigated the effect of the phylogenetic isolation of host trees on the pressure exerted by specialist and generalist enemies (parasitoids and birds) on ectophagous Lepidoptera and galling Hymenoptera. We found that the phylogenetic isolation of host trees decreases pressure by specialist enemies on these insect herbivores. In Lepidoptera, decreasing enemy pressure resulted from the density dependence of enemy attack, a mechanism often observed in herbivores. In contrast, in galling Hymenoptera, enemy pressure declined with the phylogenetic isolation of host trees per se, as well as with the parallel decline in leaf damage by non-galling insects. Our results suggest that plants that leave their phylogenetic ancestral neighborhood can trigger, partly through simple density-dependency, an enemy release and fitness increase of the few insect herbivores that succeed in tracking these plants

Do geochemical estimates of sediment focusing pass the sediment test in the equatorial Pacific?

The paleoceanographic recording fidelity of pelagic sediments is limited by chemical diagenesis and physical mixing (bioturbation and horizontal sediment transport). Diagenesis and bioturbation are relatively well-studied, but the effects of physical sedimentation have been largely ignored. Modeling U series isotopes (e.g., 230Th) can potentially quantify horizontal sediment movement, but model horizontal sediment focusing often equals or exceeds the vertical particle rain. We find no evidence of this level of sediment focusing in the equatorial Pacific from geophysical data or sediment core comparisons. The overestimate of sediment focusing by 230Th is probably caused by poor model assumptions: that sediment does not fractionate (does not sort according to size during transport) and that 230Th cannot leak from slowly accumulating sediments. Both assumptions are weak. U series methods do hold promise to quantify sediment focusing if properly calibrated. With calibration the trade-offs between seeking high sedimentation rates for better time resolution and the blurring by horizontal sediment focusing can be better assessed. Copyright 2005 by the American Geophysical Union