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Open AccessMixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling
The phenomenon of mixed/heterogenous treatment responses to cancer therapies within an individual patient presents a challenging clinical scenario. Furthermore, the molecular basis of mixed intra-patient tumor...
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Article
Open AccessA Phase Ib Study Assessing the Safety, Tolerability, and Efficacy of the First-in-Class Wee1 Inhibitor Adavosertib (AZD1775) as Monotherapy in Patients with Advanced Solid Tumors
Adavosertib (AZD1775) is a first-in-class, selective, small-molecule inhibitor of Wee1.
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Open AccessAuthor Correction: Candidate mechanisms of acquired resistance to first-line osimertinib in EGFR-mutated advanced non-small cell lung cancer
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Open AccessA phase Ib study of adavosertib, a selective Wee1 inhibitor, in patients with locally advanced or metastatic solid tumors
Adavosertib selectively inhibits Wee1, which regulates intra-S and G2/M cell-cycle checkpoints. This study investigated dosing schedules for adavosertib monotherapy, determining the maximum tolerated dose (MTD...
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Open AccessCandidate mechanisms of acquired resistance to first-line osimertinib in EGFR-mutated advanced non-small cell lung cancer
Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), potently and selectively inhibits EGFR-TKI-sensitizing and EGFR T790M resistance mutations. In the Phase III FLAURA study ...
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Open AccessAnalysis of acquired resistance mechanisms to osimertinib in patients with EGFR-mutated advanced non-small cell lung cancer from the AURA3 trial
Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), potently and selectively inhibits EGFR-TKI-sensitizing and EGFR T790M resistance mutations. This analysis evaluates acquired ...
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Open AccessClinical impact of subclonal EGFR T790M mutations in advanced-stage EGFR-mutant non-small-cell lung cancers
Advanced non-small-cell lung cancer (NSCLC) patients with EGFR T790M-positive tumours benefit from osimertinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). Here we show that the s...
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Open AccessAnalysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden
High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors and has been shown to be more significantly associated with response to PD-1 and PD-L1 blockade immuno...
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Open AccessGenomic analysis of 63,220 tumors reveals insights into tumor uniqueness and targeted cancer immunotherapy strategies
The integration of genomics with immunotherapy has potential value for cancer vaccine development. Given the clinical successes of immune checkpoint modulators, interest in cancer vaccines as therapeutic optio...
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Open AccessFGFR1 and NTRK3 actionable alterations in “Wild-Type” gastrointestinal stromal tumors
About 10–15% of adult, and most pediatric, gastrointestinal stromal tumors (GIST) lack mutations in KIT, PDGFRA, SDHx, or RAS pathway components (KRAS, BRAF, NF1). The identification of additional mutated gene...
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Comprehensive genomic profiling of inflammatory breast cancer cases reveals a high frequency of clinically relevant genomic alterations
Inflammatory breast cancer (IBC) is a distinct clinicopathologic entity that carries a worse prognosis relative to non-IBC breast cancer even when matched for standard biomarkers (ER/PR/HER2). The objective of...
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Open AccessSTUMP un“stumped”: anti-tumor response to anaplastic lymphoma kinase (ALK) inhibitor based targeted therapy in uterine inflammatory myofibroblastic tumor with myxoid features harboring DCTN1-ALK fusion
Recurrent, metastatic mesenchymal myxoid tumors of the gynecologic tract present a management challenge as there is minimal evidence to guide systemic therapy. Such tumors also present a diagnostic dilemma, as...
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Anchored multiplex PCR for targeted next-generation sequencing
Scalable and rapid target enrichment method for next-generation sequencing of clinical-grade, formalin-fixed paraffin-embedded cancer samples.
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Whole-exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors
Matthew Meyerson and colleagues report exome sequencing of solitary fibrous tumor (SFT), a rare mesenchymal tumor. They identify a NAB2-STAT6 fusion in 55% of cases.
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Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer
Epidermal growth factor receptor (EGFR)-mutant tumours define a unique subset of non-small-cell lung cancer (NSCLC). These tumours display sensitivity to small...
