Featured
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World View |
Why I pivoted from COVID-19 back to cancer research
The COVID-19 pandemic showed what can be achieved with clear goals, less bureaucracy and enough funding — important lessons for cancer research.
- Samra Turajlic
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Article
| Open Access
Detection of early seeding of Richter transformation in chronic lymphocytic leukemia
Single-cell genomic and transcriptomic analyses of longitudinal samples of patients with Richter syndrome reveal the presence and dynamics of clones driving transformation from chronic lymphocytic leukemia years before clinical manifestation
- Ferran Nadeu
- , Romina Royo
- & Elías Campo
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Article |
Limited evolution of the actionable metastatic cancer genome under therapeutic pressure
Whole-genome sequencing of metastatic biopsies longitudinally sampled during the course of anticancer treatment reveals that the actionable metastatic cancer genome remains relatively stable over time.
- Joris van de Haar
- , Louisa R. Hoes
- & Emile E. Voest
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Article |
Single-cell dissection of intratumoral heterogeneity and lineage diversity in metastatic gastric adenocarcinoma
Single-cell analysis of gastric cancer samples tracks the cell of origin of metastatic lesions and identifies an independent prognostic signature of the clinical outcome.
- Ruiping Wang
- , Minghao Dang
- & Linghua Wang
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Letter |
Geospatial immune variability illuminates differential evolution of lung adenocarcinoma
Multiregion spatial histology, exome and transcriptome data from patients with non-small cell lung cancer suggest that cancer subclones from immune cold regions diversify later than subclones from immune hot regions
- Khalid AbdulJabbar
- , Shan E. Ahmed Raza
- & Yinyin Yuan
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Article |
Regenerative lineages and immune-mediated pruning in lung cancer metastasis
Single-cell analysis of lung cancer progression uncovers developmental and regenerative programs co-opted by cancer cells and immune-mediated pruning during metastatic outbreak
- Ashley M. Laughney
- , Jing Hu
- & Joan Massagué
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Perspective |
Single-cell genomic approaches for developing the next generation of immunotherapies
Amit and colleagues discuss where single-cell genomic technologies can be applied both in trial design and in the clinical trial stage to improve the development of immunotherapies.
- Ido Yofe
- , Rony Dahan
- & Ido Amit
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Letter |
A clonal expression biomarker associates with lung cancer mortality
TRACERx Lung: Intratumoral transcriptional heterogeneity, which often hinders the development of clinically useful RNA-expression-biased biomarkers for cancer, can now be overcome with an approach for the identification of clonal expression biomarkers.
- Dhruva Biswas
- , Nicolai J. Birkbak
- & Angeles Montero
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Article |
Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma
Single cell dissection of plasma cell heterogeneity in myeloma patients reveals new insights into disease that may inform early diagnosis and clinical management.
- Guy Ledergor
- , Assaf Weiner
- & Ido Amit
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Resource |
The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space
In-depth methylation analysis of formalin-fixed paraffin-embedded glioblastoma samples demonstrates heterogeneity between primary and recurring tumors and enables prediction of composition of the tumor microenvironment and insights into progression.
- Johanna Klughammer
- , Barbara Kiesel
- & Christoph Bock
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Resource |
Phenotype molding of stromal cells in the lung tumor microenvironment
A comprehensive single-cell analysis of the lung cancer microenvironment reveals marked heterogeneity of transcriptional networks that defines novel clinically relevant stromal cell populations.
- Diether Lambrechts
- , Els Wauters
- & Bernard Thienpont
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Article |
Functional diversity and cooperativity between subclonal populations of pediatric glioblastoma and diffuse intrinsic pontine glioma cells
Genomic and functional analysis of intratumor heterogeneity in pediatric glioma uncovers early clonal divergence and stable spontaneous cooperation between subclonal populations throughout tumor evolution.
- Mara Vinci
- , Anna Burford
- & Chris Jones
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Article |
Single-cell developmental classification of B cell precursor acute lymphoblastic leukemia at diagnosis reveals predictors of relapse
Mass cytometry of diagnostic biopsies from children with B cell precursor acute lymphoblastic leukemia identifies a signaling state that predicts relapse.
- Zinaida Good
- , Jolanda Sarno
- & Kara L Davis
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Article |
Noncanonical hedgehog pathway activation through SRF–MKL1 promotes drug resistance in basal cell carcinomas
A large proportion of basal cell carcinomas develop resistance independently of the canonical mutations in genes encoding hedgehog pathway components. An unbiased analysis investigating alternative pathways of resistance uncovers the role of cytoskeletal signaling in driving noncanonical activation of hedgehog signaling through nuclear translocation of SRF and MKL1. These results advance understanding of the mechanisms underlying drug resistance and provide new actionable insights for clinical translation.
- Ramon J Whitson
- , Alex Lee
- & Anthony E Oro
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Article |
Cooperative targeting of melanoma heterogeneity with an AXL antibody-drug conjugate and BRAF/MEK inhibitors
Expression of AXL earmarks melanoma cells resistant to BRAF and MEK inhibitors that either pre-exist in treatment-naive tumors or emerge in response to therapy. The combination of an AXL-MMAE antibody-drug conjugate with BRAF and MEK inhibitors eliminates heterogeneous melanoma cell populations and prolongs survival in experimental in vivo models at tolerable toxicity. This approach is currently being tested in clinical trials and provides insights into the therapeutic targeting of intra-tumor heterogeneity.
- Julia Boshuizen
- , Louise A Koopman
- & Paul W H I Parren
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Technical Report |
Whole-genome single-cell copy number profiling from formalin-fixed paraffin-embedded samples
A method enabling copy-number analysis of single cells from formalin-fixed paraffin-embedded samples is described, validated and applied to analyze samples of synchronous ductal carcinoma in situ and invasive breast carcinoma.
- Luciano G Martelotto
- , Timour Baslan
- & Jorge S Reis-Filho
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Resource |
DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma
DNA methylation sequencing and bioinformatic analyses uncover an epigenetic disease spectrum in Ewing sarcoma. These characteristic epigenome patterns correlate with state of differentiation and disease aggressiveness, and pave the way for the development of biomarkers.
- Nathan C Sheffield
- , Gaelle Pierron
- & Eleni M Tomazou
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Article |
Distinct evolution and dynamics of epigenetic and genetic heterogeneity in acute myeloid leukemia
Genome-wide methylome sequencing of serial samples obtained from patients with acute myeloid leukemia reveals that epigenetic alleles and genetic alleles follow independent courses during disease evolution.
- Sheng Li
- , Francine E Garrett-Bakelman
- & Christopher E Mason
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Article |
Combined inhibition of DDR1 and Notch signaling is a therapeutic strategy for KRAS-driven lung adenocarcinoma
Transcriptional profiling of Kras-driven early lesions—aimed at identifying founder events—reveals DDR1 as a therapeutic target relevant to adenocarcinoma.
- Chiara Ambrogio
- , Gonzalo Gómez-López
- & Mariano Barbacid
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Letter |
Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients
By monitoring ctDNA, the authors reveal the dynamic adaption of clonal populations in colorectal cancer patients treated with anti-EGFR therapy, suggesting that therapeutic re-challenge may have some benefit.
- Giulia Siravegna
- , Benedetta Mussolin
- & Alberto Bardelli
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Article |
Studying clonal dynamics in response to cancer therapy using high-complexity barcoding
The authors have developed a barcoded library that enables the high-throughput tracking of tumor cell dynamics and clonal evolution in response to therapy.
- Hyo-eun C Bhang
- , David A Ruddy
- & Frank Stegmeier
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Between Bedside and Bench |
Tumor Heterogeneity Confounds and Illuminates: A case for Darwinian tumor evolution
- Kornelia Polyak
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Between Bedside and Bench |
Tumor Heterogeneity Confounds and Illuminates: Assessing the implications
Certain biological features are inherent traits of cancer, yet some of them still hold mysteries for researchers and clinicians. The heterogeneity of a tumor mass is an old concept that has lately become both a puzzling factor and a feature that should be harnessed to better understand tumor vulnerabilities. Improved scientific approaches to further determine and uncover the meaning of these heterogeneous features are still needed to translate findings into ways to develop therapies, identify drug response biomarkers and stratify patients. In Bedside to Bench, Maria Kleppe and Ross L. Levine look at recent clinical cancer trials that have advanced the field and discuss main questions regarding the role of tumor heterogeneity in predicting therapeutic response and tumor progression. In addition, they raise awareness of the relevance of the interactions among different tumor entities and their contribution to the malignancy of the whole tumor. In Bench to Bedside, Kornelia Polyak peruses studies that uncover specific mutations conferring endocrine drug resistance in breast tumors and that add to our knowledge of the evolution and architecture of tumors, and she discusses how this can be used to implement drug regimens.
- Maria Kleppe
- & Ross L Levine
Evolutionary characterization of lung adenocarcinoma morphology in TRACERx