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  1. Article ; Online: Mastering the use of cellular barcoding to explore cancer heterogeneity.

    Serrano, Antonin / Berthelet, Jean / Naik, Shalin H / Merino, Delphine

    Nature reviews. Cancer

    2022  Volume 22, Issue 11, Page(s) 609–624

    Abstract: Tumours are often composed of a multitude of malignant clones that are genomically unique, and only a few of them may have the ability to escape cancer therapy and grow as symptomatic lesions. As a result, tumours with a large degree of genomic diversity ...

    Abstract Tumours are often composed of a multitude of malignant clones that are genomically unique, and only a few of them may have the ability to escape cancer therapy and grow as symptomatic lesions. As a result, tumours with a large degree of genomic diversity have a higher chance of leading to patient death. However, clonal fate can be driven by non-genomic features. In this context, new technologies are emerging not only to track the spatiotemporal fate of individual cells and their progeny but also to study their molecular features using various omics analysis. In particular, the recent development of cellular barcoding facilitates the labelling of tens to millions of cancer clones and enables the identification of the complex mechanisms associated with clonal fate in different microenvironments and in response to therapy. In this Review, we highlight the recent discoveries made using lentiviral-based cellular barcoding techniques, namely genetic and optical barcoding. We also emphasize the strengths and limitations of each of these technologies and discuss some of the key concepts that must be taken into consideration when one is designing barcoding experiments. Finally, we suggest new directions to further improve the use of these technologies in cancer research.
    MeSH term(s) Humans ; Clone Cells ; Neoplasms/genetics ; Tumor Microenvironment/genetics
    Language English
    Publishing date 2022-08-18
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2062767-1
    ISSN 1474-1768 ; 1474-175X
    ISSN (online) 1474-1768
    ISSN 1474-175X
    DOI 10.1038/s41568-022-00500-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5563: Show issues Location:
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  2. Article ; Online: Experimental and spontaneous metastasis assays can result in divergence in clonal architecture.

    Serrano, Antonin / Weber, Tom / Berthelet, Jean / El-Saafin, Farrah / Gadipally, Sreeja / Charafe-Jauffret, Emmanuelle / Ginestier, Christophe / Mariadason, John M / Oakes, Samantha R / Britt, Kara / Naik, Shalin H / Merino, Delphine

    Communications biology

    2023  Volume 6, Issue 1, Page(s) 821

    Abstract: Intratumoural heterogeneity is associated with poor outcomes in breast cancer. To understand how malignant clones survive and grow in metastatic niches, in vivo models using cell lines and patient-derived xenografts (PDX) have become the gold standard. ... ...

    Abstract Intratumoural heterogeneity is associated with poor outcomes in breast cancer. To understand how malignant clones survive and grow in metastatic niches, in vivo models using cell lines and patient-derived xenografts (PDX) have become the gold standard. Injections of cancer cells in orthotopic sites (spontaneous metastasis assays) or into the vasculature (experimental metastasis assays) have been used interchangeably to study the metastatic cascade from early events or post-intravasation, respectively. However, less is known about how these different routes of injection impact heterogeneity. Herein we directly compared the clonality of spontaneous and experimental metastatic assays using the human cell line MDA-MB-231 and a PDX model. Genetic barcoding was used to study the fitness of the subclones in primary and metastatic sites. Using spontaneous assays, we found that intraductal injections resulted in less diverse tumours compared to other routes of injections. Using experimental metastasis assays via tail vein injection of barcoded MDA-MB-231 cells, we also observed an asymmetry in metastatic heterogeneity between lung and liver that was not observed using spontaneous metastasis assays. These results demonstrate that these assays can result in divergent clonal outputs in terms of metastatic heterogeneity and provide a better understanding of the biases inherent to each technique.
    MeSH term(s) Humans ; Female ; Lung Neoplasms/pathology ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Lung/pathology ; Liver/pathology ; Clone Cells/pathology
    Language English
    Publishing date 2023-08-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-023-05167-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Computational Screening of Anti-Cancer Drugs Identifies a New BRCA Independent Gene Expression Signature to Predict Breast Cancer Sensitivity to Cisplatin.

    Berthelet, Jean / Foroutan, Momeneh / Bhuva, Dharmesh D / Whitfield, Holly J / El-Saafin, Farrah / Cursons, Joseph / Serrano, Antonin / Merdas, Michal / Lim, Elgene / Charafe-Jauffret, Emmanuelle / Ginestier, Christophe / Ernst, Matthias / Hollande, Frédéric / Anderson, Robin L / Pal, Bhupinder / Yeo, Belinda / Davis, Melissa J / Merino, Delphine

    Cancers

    2022  Volume 14, Issue 10

    Abstract: The development of therapies that target specific disease subtypes has dramatically improved outcomes for patients with breast cancer. However, survival gains have not been uniform across patients, even within a given molecular subtype. Large collections ...

    Abstract The development of therapies that target specific disease subtypes has dramatically improved outcomes for patients with breast cancer. However, survival gains have not been uniform across patients, even within a given molecular subtype. Large collections of publicly available drug screening data matched with transcriptomic measurements have facilitated the development of computational models that predict response to therapy. Here, we generated a series of predictive gene signatures to estimate the sensitivity of breast cancer samples to 90 drugs, comprising FDA-approved drugs or compounds in early development. To achieve this, we used a cell line-based drug screen with matched transcriptomic data to derive in silico models that we validated in large independent datasets obtained from cell lines and patient-derived xenograft (PDX) models. Robust computational signatures were obtained for 28 drugs and used to predict drug efficacy in a set of PDX models. We found that our signature for cisplatin can be used to identify tumors that are likely to respond to this drug, even in absence of the BRCA-1 mutation routinely used to select patients for platinum-based therapies. This clinically relevant observation was confirmed in multiple PDXs. Our study foreshadows an effective delivery approach for precision medicine.
    Language English
    Publishing date 2022-05-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers14102404
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The site of breast cancer metastases dictates their clonal composition and reversible transcriptomic profile.

    Berthelet, Jean / Wimmer, Verena C / Whitfield, Holly J / Serrano, Antonin / Boudier, Thomas / Mangiola, Stefano / Merdas, Michal / El-Saafin, Farrah / Baloyan, David / Wilcox, Jordan / Wilcox, Steven / Parslow, Adam C / Papenfuss, Anthony T / Yeo, Belinda / Ernst, Matthias / Pal, Bhupinder / Anderson, Robin L / Davis, Melissa J / Rogers, Kelly L /
    Hollande, Frédéric / Merino, Delphine

    Science advances

    2021  Volume 7, Issue 28

    Abstract: Intratumoral heterogeneity is a driver of breast cancer progression, but the nature of the clonal interactive network involved in this process remains unclear. Here, we optimized the use of optical barcoding to visualize and characterize 31 cancer ... ...

    Abstract Intratumoral heterogeneity is a driver of breast cancer progression, but the nature of the clonal interactive network involved in this process remains unclear. Here, we optimized the use of optical barcoding to visualize and characterize 31 cancer subclones in vivo. By mapping the clonal composition of thousands of metastases in two clinically relevant sites, the lungs and liver, we found that metastases were highly polyclonal in lungs but not in the liver. Furthermore, the transcriptome of the subclones varied according to their metastatic niche. We also identified a reversible niche-driven signature that was conserved in lung and liver metastases collected during patient autopsies. Among this signature, we found that the tumor necrosis factor-α pathway was up-regulated in lung compared to liver metastases, and inhibition of this pathway affected metastasis diversity. These results highlight that the cellular and molecular heterogeneity observed in metastases is largely dictated by the tumor microenvironment.
    MeSH term(s) Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Female ; Humans ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Lung Neoplasms/pathology ; Neoplasm Metastasis ; Transcriptome ; Tumor Microenvironment/genetics
    Language English
    Publishing date 2021-07-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.abf4408
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Synergistic action of the MCL-1 inhibitor S63845 with current therapies in preclinical models of triple-negative and HER2-amplified breast cancer.

    Merino, Delphine / Whittle, James R / Vaillant, François / Serrano, Antonin / Gong, Jia-Nan / Giner, Goknur / Maragno, Ana Leticia / Chanrion, Maïa / Schneider, Emilie / Pal, Bhupinder / Li, Xiang / Dewson, Grant / Gräsel, Julius / Liu, Kevin / Lalaoui, Najoua / Segal, David / Herold, Marco J / Huang, David C S / Smyth, Gordon K /
    Geneste, Olivier / Lessene, Guillaume / Visvader, Jane E / Lindeman, Geoffrey J

    Science translational medicine

    2017  Volume 9, Issue 401

    Abstract: The development of BH3 mimetics, which antagonize prosurvival proteins of the BCL-2 family, represents a potential breakthrough in cancer therapy. Targeting the prosurvival member MCL-1 has been an area of intense interest because it is frequently ... ...

    Abstract The development of BH3 mimetics, which antagonize prosurvival proteins of the BCL-2 family, represents a potential breakthrough in cancer therapy. Targeting the prosurvival member MCL-1 has been an area of intense interest because it is frequently deregulated in cancer. In breast cancer, MCL-1 is often amplified, and high expression predicts poor patient outcome. We tested the MCL-1 inhibitor S63845 in breast cancer cell lines and patient-derived xenografts with high expression of MCL-1. S63845 displayed synergistic activity with docetaxel in triple-negative breast cancer and with trastuzumab or lapatinib in HER2-amplified breast cancer. Using S63845-resistant cells combined with CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated 9) technology, we identified deletion of BAK and up-regulation of prosurvival proteins as potential mechanisms that confer resistance to S63845 in breast cancer. Collectively, our findings provide a strong rationale for the clinical evaluation of MCL-1 inhibitors in breast cancer.
    MeSH term(s) Animals ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Cell Line, Tumor ; Drug Resistance, Neoplasm/drug effects ; Drug Synergism ; Female ; Gene Amplification ; Humans ; Myeloid Cell Leukemia Sequence 1 Protein/antagonists & inhibitors ; Myeloid Cell Leukemia Sequence 1 Protein/metabolism ; Pyrimidines/pharmacology ; Pyrimidines/therapeutic use ; Quinazolines/pharmacology ; Quinazolines/therapeutic use ; Receptor, ErbB-2/genetics ; Survival Analysis ; Taxoids/pharmacology ; Taxoids/therapeutic use ; Thiophenes/pharmacology ; Thiophenes/therapeutic use ; Trastuzumab/pharmacology ; Trastuzumab/therapeutic use ; Treatment Outcome ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/pathology ; Xenograft Model Antitumor Assays ; bcl-2 Homologous Antagonist-Killer Protein/metabolism ; bcl-X Protein/metabolism
    Chemical Substances Myeloid Cell Leukemia Sequence 1 Protein ; Pyrimidines ; Quinazolines ; S63845 ; Taxoids ; Thiophenes ; bcl-2 Homologous Antagonist-Killer Protein ; bcl-X Protein ; lapatinib (0VUA21238F) ; docetaxel (15H5577CQD) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Trastuzumab (P188ANX8CK)
    Language English
    Publishing date 2017-08-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.aam7049
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6941: Show issues Location:
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