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  1. Article ; Online: Hallmarks of Cancer: New Dimensions.

    Hanahan, Douglas

    Cancer discovery

    2022  Volume 12, Issue 1, Page(s) 31–46

    Abstract: The hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity of cancer phenotypes and genotypes into a provisional set of underlying principles. As knowledge of cancer mechanisms has progressed, other facets of the ... ...

    Abstract The hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity of cancer phenotypes and genotypes into a provisional set of underlying principles. As knowledge of cancer mechanisms has progressed, other facets of the disease have emerged as potential refinements. Herein, the prospect is raised that phenotypic plasticity and disrupted differentiation is a discrete hallmark capability, and that nonmutational epigenetic reprogramming and polymorphic microbiomes both constitute distinctive enabling characteristics that facilitate the acquisition of hallmark capabilities. Additionally, senescent cells, of varying origins, may be added to the roster of functionally important cell types in the tumor microenvironment. SIGNIFICANCE: Cancer is daunting in the breadth and scope of its diversity, spanning genetics, cell and tissue biology, pathology, and response to therapy. Ever more powerful experimental and computational tools and technologies are providing an avalanche of "big data" about the myriad manifestations of the diseases that cancer encompasses. The integrative concept embodied in the hallmarks of cancer is helping to distill this complexity into an increasingly logical science, and the provisional new dimensions presented in this perspective may add value to that endeavor, to more fully understand mechanisms of cancer development and malignant progression, and apply that knowledge to cancer medicine.
    MeSH term(s) Epigenomics ; Humans ; Neoplasms ; Tumor Microenvironment
    Language English
    Publishing date 2022-01-13
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2625242-9
    ISSN 2159-8290 ; 2159-8274
    ISSN (online) 2159-8290
    ISSN 2159-8274
    DOI 10.1158/2159-8290.CD-21-1059
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: "My goal is to help establish an innovative multi-institutional Lausanne cancer center within five years" Interview with Prof. Dr. Douglas Hanahan

    Heuss, A. / Hanahan, Douglas

    Schweizer Krebs-Bulletin

    2009  Volume 29, Issue 2, Page(s) 148–150

    Language English ; French ; German
    Document type Article
    ZDB-ID 1340924-4
    Database Current Contents Medicine

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  3. Article ; Online: Cancer hallmarks intersect with neuroscience in the tumor microenvironment.

    Hanahan, Douglas / Monje, Michelle

    Cancer cell

    2023  Volume 41, Issue 3, Page(s) 573–580

    Abstract: The mechanisms underlying the multistep process of tumorigenesis can be distilled into a logical framework involving the acquisition of functional capabilities, the so-called hallmarks of cancer, which are collectively envisaged to be necessary for ... ...

    Abstract The mechanisms underlying the multistep process of tumorigenesis can be distilled into a logical framework involving the acquisition of functional capabilities, the so-called hallmarks of cancer, which are collectively envisaged to be necessary for malignancy. These capabilities, embodied both in transformed cancer cells as well as in the heterotypic accessory cells that together constitute the tumor microenvironment (TME), are conveyed by certain abnormal characteristics of the cancerous phenotype. This perspective discusses the link between the nervous system and the induction of hallmark capabilities, revealing neurons and neuronal projections (axons) as hallmark-inducing constituents of the TME. We also discuss the autocrine and paracrine neuronal regulatory circuits aberrantly activated in cancer cells that may constitute a distinctive "enabling" characteristic contributing to the manifestation of hallmark functions and consequent cancer pathogenesis.
    MeSH term(s) Humans ; Tumor Microenvironment ; Neoplasms/pathology ; Carcinogenesis ; Neurons/pathology
    Language English
    Publishing date 2023-03-14
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2078448-X
    ISSN 1878-3686 ; 1535-6108
    ISSN (online) 1878-3686
    ISSN 1535-6108
    DOI 10.1016/j.ccell.2023.02.012
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  4. Article ; Online: Swiss Medical Weekly congratulates Jaco van Rheenen, recipient of the Dr Josef Steiner Cancer Research Foundation Award for 2017.

    Hanahan, Douglas

    Swiss medical weekly

    2017  Volume 147, Page(s) w14542

    MeSH term(s) Awards and Prizes ; Humans
    Language English
    Publishing date 2017
    Publishing country Switzerland
    Document type Journal Article ; Comment
    ZDB-ID 2036179-8
    ISSN 1424-3997 ; 1424-7860
    ISSN (online) 1424-3997
    ISSN 1424-7860
    DOI 10.4414/smw.2017.14542
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  5. Article ; Online: Rethinking the war on cancer.

    Hanahan, Douglas

    Lancet (London, England)

    2014  Volume 383, Issue 9916, Page(s) 558–563

    Abstract: Some 40 years ago a metaphor was posed that cancer was such an insidious adversary that a declaration of war on the disease was justified. Although this statement was a useful inspiration for enlistment of resources, despite extraordinary progress in our ...

    Abstract Some 40 years ago a metaphor was posed that cancer was such an insidious adversary that a declaration of war on the disease was justified. Although this statement was a useful inspiration for enlistment of resources, despite extraordinary progress in our understanding of disease pathogenesis, in most cases and for most forms of cancer this war has not been won. A second metaphor was about magic bullets--targeted therapies based on knowledge of mechanisms that were envisaged to strike with devastating consequences for the disease. The reality, however, is that targeted therapies are generally not curative or even enduringly effective, because of the adaptive and evasive resistance strategies developed by cancers under attack. In this Series paper, I suggest that, much like in modern warfare, the war on cancer needs to have a battlespace vision.
    MeSH term(s) Anticarcinogenic Agents/therapeutic use ; Antineoplastic Agents/therapeutic use ; Health Planning ; Humans ; Metaphor ; Molecular Targeted Therapy ; Neoplasms/prevention & control
    Chemical Substances Anticarcinogenic Agents ; Antineoplastic Agents
    Language English
    Publishing date 2014-02-08
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0023-7507 ; 0140-6736
    ISSN (online) 1474-547X
    ISSN 0023-7507 ; 0140-6736
    DOI 10.1016/S0140-6736(13)62226-6
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  6. Book: Perspectives on the molecular biology and immunology of the pancreatic-beta-cell

    Hanahan, Douglas

    (Current communications in molecular biology)

    1989  

    Author's details ed. by Douglas Hanahan
    Series title Current communications in molecular biology
    Keywords Islets of Langerhans / immunology ; Diabetes Mellitus / genetics ; Bauchspeicheldrüse ; B-Zelle ; Molekularbiologie ; Immunologie
    Subject Klinische Immunologie ; Beta-Zelle ; Pankreas ; Molekulare Biologie
    Size XI, 212 S. : Ill., graph. Darst.
    Publisher Cold Spring Harbor Laboratory
    Publishing place New York, NY
    Publishing country United States
    Document type Book
    HBZ-ID HT003499019
    ISBN 0-87969-326-6 ; 978-0-87969-326-8
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    1990 B 687 order for loan Magazin

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  7. Article ; Online: A Subset of Cancer-Associated Fibroblasts Determines Therapy Resistance.

    Huelsken, Joerg / Hanahan, Douglas

    Cell

    2018  Volume 172, Issue 4, Page(s) 643–644

    Abstract: While functional heterogeneity of fibroblastic cells populating the tumor microenvironment is increasingly recognized, lack of definitive markers complicates elucidation of roles among ostensibly distinctive fibroblastic states. In this issue of Cell, Su ...

    Abstract While functional heterogeneity of fibroblastic cells populating the tumor microenvironment is increasingly recognized, lack of definitive markers complicates elucidation of roles among ostensibly distinctive fibroblastic states. In this issue of Cell, Su et al. characterize a new pro-tumorigenic cancer-associated fibroblast subset mediating chemoresistance defined and driven by a novel signaling pathway.
    MeSH term(s) Cancer-Associated Fibroblasts ; Carcinogenesis ; Fibroblasts ; Humans ; Signal Transduction ; Tumor Microenvironment
    Language English
    Publishing date 2018-02-20
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2018.01.028
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  8. Article ; Online: A set of microRNAs coordinately controls tumorigenesis, invasion, and metastasis.

    Michael, Iacovos P / Saghafinia, Sadegh / Hanahan, Douglas

    Proceedings of the National Academy of Sciences of the United States of America

    2019  Volume 116, Issue 48, Page(s) 24184–24195

    Abstract: MicroRNA-mediated gene regulation has been implicated in various diseases, including cancer. This study examined the role of microRNAs (miRNAs) during tumorigenesis and malignant progression of pancreatic neuroendocrine tumors (PanNETs) in a genetically ... ...

    Abstract MicroRNA-mediated gene regulation has been implicated in various diseases, including cancer. This study examined the role of microRNAs (miRNAs) during tumorigenesis and malignant progression of pancreatic neuroendocrine tumors (PanNETs) in a genetically engineered mouse model. Previously, a set of miRNAs was observed to be specifically up-regulated in a highly invasive and metastatic subtype of mouse and human PanNET. Using functional assays, we now implicate different miRNAs in distinct phenotypes: miR-137 stimulates tumor growth and local invasion, whereas the miR-23b cluster enables metastasis. An algorithm, Bio-miRTa, has been developed to facilitate the identification of biologically relevant miRNA target genes and applied to these miRNAs. We show that a top-ranked miR-137 candidate gene,
    MeSH term(s) Activin Receptors, Type I/genetics ; Activins/genetics ; Algorithms ; Animals ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; Computational Biology/methods ; Doxycycline/pharmacology ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; LDL-Receptor Related Proteins/genetics ; Liver Neoplasms/genetics ; Liver Neoplasms/secondary ; Membrane Transport Proteins/genetics ; Mice ; MicroRNAs/genetics ; Neuroendocrine Tumors/genetics ; Neuroendocrine Tumors/mortality ; Neuroendocrine Tumors/pathology ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/mortality ; Pancreatic Neoplasms/pathology ; Prognosis ; Receptors, LDL/genetics ; Xenograft Model Antitumor Assays
    Chemical Substances LDL-Receptor Related Proteins ; Membrane Transport Proteins ; MicroRNAs ; Receptors, LDL ; SORL1 protein, human ; Sorl1 protein, mouse ; activin B ; Activins (104625-48-1) ; ACVR1C protein, human (EC 2.7.11.30) ; Activin Receptors, Type I (EC 2.7.11.30) ; Doxycycline (N12000U13O)
    Language English
    Publishing date 2019-11-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1913307116
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  9. Article ; Online: Cancer cell autophagy, reprogrammed macrophages, and remodeled vasculature in glioblastoma triggers tumor immunity.

    Chryplewicz, Agnieszka / Scotton, Julie / Tichet, Mélanie / Zomer, Anoek / Shchors, Ksenya / Joyce, Johanna A / Homicsko, Krisztian / Hanahan, Douglas

    Cancer cell

    2022  Volume 40, Issue 10, Page(s) 1111–1127.e9

    Abstract: Glioblastoma (GBM) is poorly responsive to therapy and invariably lethal. One conceivable strategy to circumvent this intractability is to co-target distinctive mechanistic components of the disease, aiming to concomitantly disrupt multiple capabilities ... ...

    Abstract Glioblastoma (GBM) is poorly responsive to therapy and invariably lethal. One conceivable strategy to circumvent this intractability is to co-target distinctive mechanistic components of the disease, aiming to concomitantly disrupt multiple capabilities required for tumor progression and therapeutic resistance. We assessed this concept by combining vascular endothelial growth factor (VEGF) pathway inhibitors that remodel the tumor vasculature with the tricyclic antidepressant imipramine, which enhances autophagy in GBM cancer cells and unexpectedly reprograms immunosuppressive tumor-associated macrophages via inhibition of histamine receptor signaling to become immunostimulatory. While neither drug is efficacious as monotherapy, the combination of imipramine with VEGF pathway inhibitors orchestrates the infiltration and activation of CD8 and CD4 T cells, producing significant therapeutic benefit in several GBM mouse models. Inclusion up front of immune-checkpoint blockade with anti-programmed death-ligand 1 (PD-L1) in eventually relapsing tumors markedly extends survival benefit. The results illustrate the potential of mechanism-guided therapeutic co-targeting of disparate biological vulnerabilities in the tumor microenvironment.
    MeSH term(s) Animals ; Antidepressive Agents, Tricyclic/metabolism ; Antidepressive Agents, Tricyclic/therapeutic use ; Autophagy ; B7-H1 Antigen/metabolism ; Glioblastoma/pathology ; Imipramine/metabolism ; Imipramine/therapeutic use ; Immune Checkpoint Inhibitors ; Immunotherapy ; Macrophages/metabolism ; Mice ; Neoplasm Recurrence, Local/drug therapy ; Programmed Cell Death 1 Receptor ; Tumor Microenvironment ; Vascular Endothelial Growth Factor A/metabolism
    Chemical Substances Antidepressive Agents, Tricyclic ; B7-H1 Antigen ; Immune Checkpoint Inhibitors ; Programmed Cell Death 1 Receptor ; Vascular Endothelial Growth Factor A ; Imipramine (OGG85SX4E4)
    Language English
    Publishing date 2022-09-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2078448-X
    ISSN 1878-3686 ; 1535-6108
    ISSN (online) 1878-3686
    ISSN 1535-6108
    DOI 10.1016/j.ccell.2022.08.014
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  10. Article ; Online: Bispecific PD1-IL2v and anti-PD-L1 break tumor immunity resistance by enhancing stem-like tumor-reactive CD8

    Tichet, Mélanie / Wullschleger, Stephan / Chryplewicz, Agnieszka / Fournier, Nadine / Marcone, Rachel / Kauzlaric, Annamaria / Homicsko, Krisztian / Deak, Laura Codarri / Umaña, Pablo / Klein, Christian / Hanahan, Douglas

    Immunity

    2023  Volume 56, Issue 1, Page(s) 162–179.e6

    Abstract: Immunotherapies have shown remarkable, albeit tumor-selective, therapeutic benefits in the clinic. Most patients respond transiently at best, highlighting the importance of understanding mechanisms underlying resistance. Herein, we evaluated the effects ... ...

    Abstract Immunotherapies have shown remarkable, albeit tumor-selective, therapeutic benefits in the clinic. Most patients respond transiently at best, highlighting the importance of understanding mechanisms underlying resistance. Herein, we evaluated the effects of the engineered immunocytokine PD1-IL2v in a mouse model of de novo pancreatic neuroendocrine cancer that is resistant to checkpoint and other immunotherapies. PD1-IL2v utilizes anti-PD-1 as a targeting moiety fused to an immuno-stimulatory IL-2 cytokine variant (IL2v) to precisely deliver IL2v to PD-1
    MeSH term(s) Animals ; Mice ; B7-H1 Antigen/immunology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Disease Models, Animal ; Immunotherapy/methods ; Macrophages/immunology ; Macrophages/metabolism ; Neoplasms/therapy ; Tumor Microenvironment ; Antibodies, Bispecific/immunology ; Interleukin-2 ; Programmed Cell Death 1 Receptor/immunology
    Chemical Substances B7-H1 Antigen ; Antibodies, Bispecific ; Interleukin-2 ; Programmed Cell Death 1 Receptor
    Language English
    Publishing date 2023-01-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2022.12.006
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