The current international cancer genomic sequencing landscape

BACKGROUND:

While next generation sequencing has enhanced our understanding of the biological basis of malignancy, current knowledge on global practices for sequencing cancer samples is limited. To address this deficiency, we developed a survey to provide a snapshot of current sequencing activities globally, identify barriers to data sharing and use this information to develop sustainable solutions for the cancer research community.

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A Landscape of Pharmacogenomic Interactions in Cancer

Research published in Cell on July 7th has shown that patient-derived cancer cell lines harbor most of the same genetic changes found in patients’ tumors, and could be used to learn how tumors are likely to respond to new drugs, increasing the success rate for developing new personalized cancer treatments.

Scientists from the Netherlands Cancer Institute (NKI), the Wellcome Trust Sanger Institute (WTSI), and the European Bioinformatics Institute (EMBL-EBI) discovered a strong link between many of the mutations commonly found in patient cancer samples and sensitivity to specific anti-cancer drugs.

In this systematic, large-scale study, the researchers combined molecular data from tumors and cancer cell lines with drug sensitivity measurements. First, they identified molecular alterations strongly associated with cancer in more than 11,000 tumors across 29 different tumor types. Then they mapped these cancer relevant alterations onto 1000 cancer cell lines and determined whether these alterations explain the response of the cell lines to 265 anti-cancer drugs.

‘These data will help advance personalized cancer medicine by guiding researchers towards cancer specific molecular alterations that clearly associate with drug sensitivity. After further validation, this will allow the creation of clinical trials specifically tailored to well-defined subgroups of patients. Ultimately, this will inform the scientific community about potential anti-cancer drugs given a molecular profile of a tumor’, says joint first author of the study Dr Daniel J. Vis, research fellow at the NKI.

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Estimating IC50 values

Recently I published a paper on the estimation of IC50 values. The central idea is that it is better to estimate the sensitivity of all items (here, cell lines / compounds) simultaneously compared to one-by-one. This allows us to borrow strength across all the observations and thereby improve stability and accuracy of the estimates. This page intends to give a high-level overview of the proposed method, the peer reviewed publication can be found here (PMID 27180993, Pharmacogenomics, May 2016, Vol. 17, No. 7, Pages 691-700). The associated script/computer code can be found here.

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