27 Result(s)
within
David B. Solit
Biomedicine
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Article
Neoplasia risk in patients with Lynch syndrome treated with immune checkpoint blockade
Metastatic and localized mismatch repair-deficient (dMMR) tumors are exquisitely sensitive to immune checkpoint blockade (ICB). The ability of ICB to prevent dMMR malignant or pre-malignant neoplasia developme...
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Clonal evolution during metastatic spread in high-risk neuroblastoma
Patients with high-risk neuroblastoma generally present with widely metastatic disease and often relapse despite intensive therapy. As most studies to date focused on diagnosis-relapse pairs, our understanding...
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Overall survival with circulating tumor DNA-guided therapy in advanced non-small-cell lung cancer
Circulating tumor DNA (ctDNA) sequencing guides therapy decisions but has been studied mostly in small cohorts without sufficient follow-up to determine its influence on overall survival. We prospectively foll...
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Genomic and transcriptomic determinants of response to neoadjuvant therapy in rectal cancer
The incidence of rectal cancer is increasing in patients younger than 50 years. Locally advanced rectal cancer is still treated with neoadjuvant radiation, chemotherapy and surgery, but recent evidence suggest...
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Article
Correction: Natural history, response to systemic therapy, and genomic landscape of plasmacytoid urothelial carcinoma
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The context-specific role of germline pathogenicity in tumorigenesis
Human cancers arise from environmental, heritable and somatic factors, but how these mechanisms interact in tumorigenesis is poorly understood. Studying 17,152 prospectively sequenced patients with cancer, we ...
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Clinical cancer genomic profiling
Technological innovation and rapid reduction in sequencing costs have enabled the genomic profiling of hundreds of cancer-associated genes as a component of routine cancer care. Tumour genomic profiling can re...
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Open AccessTumor fraction-guided cell-free DNA profiling in metastatic solid tumor patients
Cell-free DNA (cfDNA) profiling is increasingly used to guide cancer care, yet mutations are not always identified. The ability to detect somatic mutations in plasma depends on both assay sensitivity and the f...
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Open AccessNatural history, response to systemic therapy, and genomic landscape of plasmacytoid urothelial carcinoma
Plasmacytoid urothelial carcinoma (PUC) is a rare, aggressive histologic variant of urothelial cancer characterised by a diffuse growth pattern and CDH1 mutation. We studied the efficacy of preoperative platinum-...
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Article
The association between tumor mutational burden and prognosis is dependent on treatment context
In multiple cancer types, high tumor mutational burden (TMB) is associated with longer survival after treatment with immune checkpoint inhibitors (ICIs). The association of TMB with survival outside of the imm...
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Open AccessPhase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer
Treatment options for triple-negative breast cancer remain limited. Activation of the PI3K pathway via loss of PTEN and/or INPP4B is common. Buparlisib is an orally bioavailable, pan-class I PI3K inhibitor. We ev...
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Cancer therapy shapes the fitness landscape of clonal hematopoiesis
Acquired mutations are pervasive across normal tissues. However, understanding of the processes that drive transformation of certain clones to cancer is limited. Here we study this phenomenon in the context of...
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High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants
Accurate identification of tumor-derived somatic variants in plasma circulating cell-free DNA (cfDNA) requires understanding of the various biological compartments contributing to the cfDNA pool. We sought to ...
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Article
Activating mutations in CSF1R and additional receptor tyrosine kinases in histiocytic neoplasms
Histiocytoses are clonal hematopoietic disorders frequently driven by mutations map** to the BRAF and MEK1 and MEK2 kinases. Currently, however, the developmental origins of histiocytoses in patients are not...
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Open AccessPIK3CA and MAP3K1 alterations imply luminal A status and are associated with clinical benefit from pan-PI3K inhibitor buparlisib and letrozole in ER+ metastatic breast cancer
Clinical trials have demonstrated the efficacy of combining phosphoinositide 3-kinase (PI3K) inhibitors with endocrine therapies in hormone therapy-refractory breast cancer. However, biomarkers of PI3K pathway...
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Tumor mutational load predicts survival after immunotherapy across multiple cancer types
Immune checkpoint inhibitor (ICI) treatments benefit some patients with metastatic cancers, but predictive biomarkers are needed. Findings in selected cancer types suggest that tumor mutational burden (TMB) ma...
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Clinical tumour sequencing for precision oncology: time for a universal strategy
Routine, comprehensive molecular characterization of patient tumours has the potential to accelerate therapeutic advances and inform cancer biology. Here, we describe insights from the implementation of an ent...
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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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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...
