Identifying robust, patient-specific, and predictive biomarkers presents a major obstacle in precision oncology. To optimize patient-specific therapeutic strategies, here we couple pathway knowledge with large-scale drug sensitivity, RNAi, and CRISPR-Cas9 screening data from 460 cell lines. Pathway activity levels are found to be strong predictive biomarkers for the essentiality of 15 proteins, including the essentiality of MAD2L1 in breast cancer patients with high BRCA-pathway activity. We also find strong predictive biomarkers for the sensitivity to 31 compounds, including BCL2 and microtubule inhibitors (MTIs). Lastly, we show that Bcl-xL inhibition can modulate the activity of a predictive biomarker pathway and resensitize lung cancer cells and tumors to MTI therapy. Overall, our results support the use of pathways in helping to achieve the goal of precision medicine by uncovering dozens of predictive biomarkers.
Modified EVAC technique as described is feasible and safe. To the best of our knowledge, this is the first description of this technique. The technique allows easier sponge placement and exchange compared to traditional EVAC technique, and allows oral intake during treatment.
IgG avidity above 65% is a good indicator of past infection, and thus excludes CMV in the amniotic fluid. In such circumstances, invasive prenatal diagnosis may eventually not be required. This optimistic conclusion, however, needs to be confirmed by large scale studies.
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