Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma

Science, Journal Year: 2014, Volume and Issue: 344(6190), P. 1396 - 1401

Published: June 13, 2014

Human cancers are complex ecosystems composed of cells with distinct phenotypes, genotypes, and epigenetic states, but current models do not adequately reflect tumor composition in patients. We used single-cell RNA sequencing (RNA-seq) to profile 430 from five primary glioblastomas, which we found be inherently variable their expression diverse transcriptional programs related oncogenic signaling, proliferation, complement/immune response, hypoxia. also observed a continuum stemness-related states that enabled us identify putative regulators stemness vivo. Finally, show established glioblastoma subtype classifiers variably expressed across individual within demonstrate the potential prognostic implications such intratumoral heterogeneity. Thus, reveal previously unappreciated heterogeneity regulatory central biology, prognosis, therapy.

Language: Английский

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Roles of the immune system in cancer: from tumor initiation to metastatic progression

Genes & Development, Journal Year: 2018, Volume and Issue: 32(19-20), P. 1267 - 1284

Published: Oct. 1, 2018

The presence of inflammatory immune cells in human tumors raises a fundamental question oncology: How do cancer avoid the destruction by attack? In principle, tumor development can be controlled cytotoxic innate and adaptive cells; however, as develops from neoplastic tissue to clinically detectable tumors, evolve different mechanisms that mimic peripheral tolerance order tumoricidal attack. Here, we provide an update recent accomplishments, unifying concepts, future challenges study tumor-associated cells, with emphasis on metastatic carcinomas.

Language: Английский

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Rethinking cancer nanotheranostics

Nature Reviews Materials, Journal Year: 2017, Volume and Issue: 2(7)

Published: May 9, 2017

Language: Английский

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The MAPK pathway across different malignancies: A new perspective

Cancer, Journal Year: 2014, Volume and Issue: 120(22), P. 3446 - 3456

Published: June 19, 2014

The mitogen‐activated protein kinase/extracellular signal‐regulated (MAPK/ERK) pathway is activated by upstream genomic events and/or activation of multiple signaling in which information coalesces at this important nodal point. This tightly regulated under normal conditions phosphatases and bidirectional communication with other pathways, like the kinase B/mammalian target rapamycin (AKT/m‐TOR) pathway. Recent evidence indicates that MAPK/ERK node can function as a tumor suppressor well more common pro‐oncogenic signal. effect predominates depends on intensity signal context or tissue aberrantly activated. Genomic profiling tumors has revealed mutations components, such v‐raf murine sarcoma viral oncogene homolog B1 ( BRAF ). Currently approved for treatment melanoma, inhibitors are being studied alone combination MAPK pathways to optimize many types. Therapies targeted toward components have various response rates when used different solid tumors, colorectal cancer ovarian cancer. Understanding differential nature each type critical developing single regimens, because unique mechanisms primary secondary subsequent sensitivity drugs. Cancer 2014;120:3446–3456. © 2014 American Society .

Language: Английский

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The single-cell pathology landscape of breast cancer

Nature, Journal Year: 2020, Volume and Issue: 578(7796), P. 615 - 620

Published: Jan. 20, 2020

Language: Английский

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Molecular profiling for precision cancer therapies

Genome Medicine, Journal Year: 2020, Volume and Issue: 12(1)

Published: Jan. 14, 2020

Abstract The number of druggable tumor-specific molecular aberrations has grown substantially in the past decade, with a significant survival benefit obtained from biomarker matching therapies several cancer types. Molecular pathology therefore become fundamental not only to inform on tumor diagnosis and prognosis but also drive therapeutic decisions daily practice. introduction next-generation sequencing technologies rising large-scale profiling programs across institutions worldwide have revolutionized field precision oncology. As comprehensive genomic analyses increasingly available both clinical research settings, healthcare professionals are faced complex tasks result interpretation translation. This review summarizes current upcoming approaches implement medicine, highlighting challenges potential solutions facilitate maximize utility results. We describe novel characterization strategies beyond DNA sequencing, such as transcriptomics, immunophenotyping, epigenetic profiling, single-cell analyses. applications liquid biopsies evaluate blood-based biomarkers, circulating cells nucleic acids. Last, lessons learned existing limitations genotype-derived provide insights into ways expand medicine genomics.

Language: Английский

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Single-cell barcoding and sequencing using droplet microfluidics

Nature Protocols, Journal Year: 2016, Volume and Issue: 12(1), P. 44 - 73

Published: Dec. 8, 2016

Language: Английский

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Genetics and biology of prostate cancer

Genes & Development, Journal Year: 2018, Volume and Issue: 32(17-18), P. 1105 - 1140

Published: Sept. 1, 2018

Despite the high long-term survival in localized prostate cancer, metastatic cancer remains largely incurable even after intensive multimodal therapy. The lethality of advanced disease is driven by lack therapeutic regimens capable generating durable responses setting extreme tumor heterogeneity on genetic and cell biological levels. Here, we review available model systems, genome atlas, cellular functional microenvironment, tumor-intrinsic tumor-extrinsic mechanisms underlying resistance, technological advances focused detection management. These advances, along with an improved understanding adaptive to conventional therapies, anti-androgen therapy, immunotherapy, are catalyzing development more effective strategies for disease. In particular, knowledge heterotypic interactions between coevolution host cells microenvironment has illuminated novel combinations a strong potential eventual cures Improved management will also benefit from artificial intelligence-based expert decision support systems proper standard care, prognostic determinant biomarkers minimize overtreatment disease, new standards care accelerated next-generation clinical trials.

Language: Английский

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Clinical management of breast cancer heterogeneity

Nature Reviews Clinical Oncology, Journal Year: 2015, Volume and Issue: 12(7), P. 381 - 394

Published: April 21, 2015

Language: Английский

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Tumor Heterogeneity in Breast Cancer

Frontiers in Medicine, Journal Year: 2017, Volume and Issue: 4

Published: Dec. 8, 2017

Breast cancer is a heterogeneous disease and differs greatly among different patients (intertumor heterogeneity) even within each individual tumor (intratumor heterogeneity). Clinical morphologic intertumor heterogeneity reflected by staging systems histopathologic classification of breast cancer. Heterogeneity in the expression established prognostic predictive biomarkers, hormone receptors HER2 oncoprotein, basis for targeted treatment. Molecular classifications are indicators genetic heterogeneity, which probed with multigene assays can lead to improved stratification into low high risk groups personalized therapy. Intratumor occurs at morphologic, genomic, transcriptomic proteomic levels, creating diagnostic therapeutic challenges. Understanding molecular cellular mechanisms that relevant development treatment resistance major area research. Despite knowledge complex phenotypic features underpinning there has been only limited advancement diagnostic, or strategies The current guidelines reporting biomarkers aim maximize patient eligibility therapy, but do not take account intratumor heterogeneity. implemented routine clinical practice. Additional studies in-depth analysis required understand significance rapidly accumulating data. This review highlights inter- carcinoma special emphasis on pathologic findings, provides insights

Language: Английский

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