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Circulating tumor DNA (ctDNA) is a promising biomarker for noninvasive assessment of cancer burden, but existing ctDNA detection methods have insufficient sensitivity or patient coverage for broad clinical applicability. Here we introduce cancer personalized profiling by deep sequencing (CAPP-Seq), an economical and ultrasensitive method for quantifying(More)
PURPOSE Ipilimumab, which is an anti-cytotoxic T-cell lymphocyte-4 monoclonal antibody, showed a survival benefit in melanoma with adverse events (AEs) managed by protocol-defined guidelines. A phase II study in lung cancer assessed the activity of ipilimumab plus paclitaxel and carboplatin. PATIENTS AND METHODS Patients (N = 204) with chemotherapy-naive(More)
High-throughput sequencing of circulating tumor DNA (ctDNA) promises to facilitate personalized cancer therapy. However, low quantities of cell-free DNA (cfDNA) in the blood and sequencing artifacts currently limit analytical sensitivity. To overcome these limitations, we introduce an approach for integrated digital error suppression (iDES). Our method(More)
The NFAT family of transcription factors is required for the expression of numerous immunologically important genes and plays a pivotal role in both the initiation and coordination of the immune response. NFAT family members appear to be regulated primarily at the level of their subcellular localization. Here we show that NFATc is additionally regulated at(More)
The calcineurin/nuclear factor of activated T cells (NFAT) signaling pathway is best known for its role in T lymphocyte activation. However, it has become increasingly apparent that this signaling pathway is also involved in the regulation of cell growth and development in a wide variety of different tissues and cell types. Here we have investigated the(More)
UNLABELLED Small cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with high mortality. We used a systematic drug repositioning bioinformatics approach querying a large compendium of gene expression profiles to identify candidate U.S. Food and Drug Administration (FDA)-approved drugs to treat SCLC. We found that tricyclic(More)
The last decade has witnessed the development of oncogene-directed targeted therapies that have significantly changed the treatment of non-small-cell lung cancer (NSCLC). In this paper we review the data demonstrating efficacy of gefitinib, erlotinib, and afatinib, which target the epidermal growth factor receptor (EGFR), and crizotinib which targets(More)
Circulating tumour DNA (ctDNA) analysis facilitates studies of tumour heterogeneity. Here we employ CAPP-Seq ctDNA analysis to study resistance mechanisms in 43 non-small cell lung cancer (NSCLC) patients treated with the third-generation epidermal growth factor receptor (EGFR) inhibitor rociletinib. We observe multiple resistance mechanisms in 46% of(More)
UNLABELLED Rociletinib is a third-generation EGFR inhibitor active in lung cancers with T790M, the gatekeeper mutation underlying most first-generation EGFR drug resistance. We biopsied patients at rociletinib progression to explore resistance mechanisms. Among 12 patients with T790M-positive cancers at rociletinib initiation, six had T790-wild-type(More)
INTRODUCTION This investigator-initiated study explores the safety, maximum tolerated dose, clinical response, and pharmacokinetics of hydroxychloroquine (HCQ) with and without erlotinib in patients with advanced non-small-cell lung cancer. METHODS Patients with prior clinical benefit from an epidermal growth factor receptor (EGFR) tyrosine kinase(More)