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Article
Open AccessConvergent evolution of BRCA2 reversion mutations under therapeutic pressure by PARP inhibition and platinum chemotherapy
Reversion mutations that restore wild-type function of the BRCA gene have been described as a key mechanism of resistance to Poly(ADP-ribose) polymerase (PARP) inhibitor therapy in BRCA-associated cancers. Here, ...
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Article
Open AccessReversion mutations in germline BRCA1/2-mutant tumors reveal a BRCA-mediated phenotype in non-canonical histologies
The association between loss of BRCA1/2 and a homologous recombination deficiency phenotype is lineage dependent. In BRCA-associated cancers such as breast, ovarian, pancreas and prostate, this phenotype confers ...
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Article
Open AccessAKT mutant allele-specific activation dictates pharmacologic sensitivities
AKT- a key molecular regulator of PI-3K signaling pathway, is somatically mutated in diverse solid cancer types, and aberrant AKT activation promotes altered cancer cell growth, survival, and metabolism1–8. The m...
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Article
NTRK1 Fusions identified by non-invasive plasma next-generation sequencing (NGS) across 9 cancer types
Activating fusions of the NTRK1, NTRK2 and NTRK3 genes are drivers of carcinogenesis and proliferation across a broad range of tumour types in both adult and paediatric patients. Recently, the FDA granted tumour-...
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Article
Author Correction: COVID-19 vaccine guidance for patients with cancer participating in oncology clinical trials
A Correction to this paper has been published: https://doi.org/10.1038/s41571-021-00503-2.
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COVID-19 vaccine guidance for patients with cancer participating in oncology clinical trials
Emerging efficacy data have led to the emergency use authorization or approval of COVID-19 vaccines in several countries worldwide. Most trials of COVID-19 vaccines excluded patients with active malignancies, ...
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Article
Open AccessSelective AKT kinase inhibitor capivasertib in combination with fulvestrant in PTEN-mutant ER-positive metastatic breast cancer
Five to ten percent of ER+ metastatic breast cancer (MBC) tumors harbor somatic PTEN mutations. Loss of function of this tumor-suppressor gene defines a highly aggressive, treatment-refractory disease for which n...
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Article
Discovery through clinical sequencing in oncology
The molecular characterization of tumors now informs clinical cancer care for many patients. This advent of molecular oncology has been driven by the expanding number of therapeutic biomarkers that can predict...
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Article
Resistance to TRK inhibition mediated by convergent MAPK pathway activation
TRK fusions are found in a variety of cancer types, lead to oncogenic addiction, and strongly predict tumor-agnostic efficacy of TRK inhibition1–8. With the recent approval of the first selective TRK inhibitor, l...
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Article
Author Correction: HER kinase inhibition in patients with HER2- and HER3-mutant cancers
The ‘Competing interests’ statement of this Article has been updated; please see the accompanying Amendment. The original Article has not been corrected online.
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Open AccessA phase Ib dose-escalation and expansion study of the oral MEK inhibitor pimasertib and PI3K/MTOR inhibitor voxtalisib in patients with advanced solid tumours
This phase Ib study evaluated the safety, maximum-tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and preliminary efficacy of pimasertib (MSC1936369B), a MEK1/2 inhibitor, in combination with voxtali...
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Article
Genome doubling shapes the evolution and prognosis of advanced cancers
Ploidy abnormalities are a hallmark of cancer, but their impact on the evolution and outcomes of cancers is unknown. Here, we identified whole-genome doubling (WGD) in the tumors of nearly 30% of 9,692 prospec...
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Article
HER kinase inhibition in patients with HER2- and HER3-mutant cancers
Somatic mutations of ERBB2 and ERBB3 (which encode HER2 and HER3, respectively) are found in a wide range of cancers. Preclinical modelling suggests that a subset of these mutations lead to constitutive HER2 acti...
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Article
Fusions in solid tumours: diagnostic strategies, targeted therapy, and acquired resistance
Oncogenic gene fusions are common in patients with solid tumours and occur across a wide spectrum of tumour types
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Erratum: Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients
Nat. Med. 23, 703–713 (2017); published online 08 May 2017; corrected after print 14 June 2017 In the version of this article initially published online, the top value in the y axis of the Kaplan–Meier plots i...
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Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients
MSK-IMPACT is a clinical sequencing platform able to detect genomic mutations, copy number alterations and structural variants in a panel of cancer-related genes. This assay is implemented prospectively to inf...
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Article
A germline JAK2 SNP is associated with predisposition to the development of JAK2V617F-positive myeloproliferative neoplasms
Ross Levine and colleagues report that the JAK2V617F somatic mutation that drives the development of chronic myeloproliferative neoplasms is associated with the presence of a specific inherited SNP in JAK2.
