Full Text Journal Articles by
Author Robert A. Weinberg


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Genetically Defined Syngeneic Mouse Models of Ovarian Cancer as Tools for the Discovery of Combination Immunotherapy.

Sonia Iyer, Shuang Zhang, Simge Yucel, Heiko Horn, Sean G Smith, Ferenc Reinhardt, Esmee Hoefsmit, Bimarzhan Assatova, Julia Casado, Marie-Charlotte Meinsohn, M Inmaculada Barrasa, George W Bell, Fernando Pérez-Villatoro, Kaisa Huhtinen, Johanna Hynninen, Jaana Oikkonen, Pamoda M Galhenage, Shailja Pathania, Paula T Hammond, Benjamin G Neel, Anniina Farkkila, David Pépin, Robert A Weinberg,

Despite advances in immuno-oncology, the relationship between tumor genotypes and response to immunotherapy remains poorly understood, particularly in high-grade serous tubo-ovarian carcinomas (HGSC). We developed a series of mouse models that carry genotypes of human HGSCs and grow in syngeneic immunocompetent hosts to address this gap. We transformed murine-fallopian tube ... Read more >>

Cancer Discov (Cancer discovery)
[2021, 11(2):384-407]

Cited: 9 times

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Genetically Defined, Syngeneic Organoid Platform for Developing Combination Therapies for Ovarian Cancer.

Shuang Zhang, Sonia Iyer, Hao Ran, Igor Dolgalev, Shengqing Gu, Wei Wei, Connor J R Foster, Cynthia A Loomis, Narciso Olvera, Fanny Dao, Douglas A Levine, Robert A Weinberg, Benjamin G Neel,

The paucity of genetically informed, immunocompetent tumor models impedes evaluation of conventional, targeted, and immune therapies. By engineering mouse fallopian tube epithelial organoids using lentiviral gene transduction and/or CRISPR/Cas9 mutagenesis, we generated multiple high-grade serous tubo-ovarian cancer (HGSC) models exhibiting mutational combinations seen in patients with HGSC. Detailed analysis of ... Read more >>

Cancer Discov (Cancer discovery)
[2021, 11(2):362-383]

Cited: 8 times

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Plasticity of ether lipids promotes ferroptosis susceptibility and evasion.

Yilong Zou, Whitney S Henry, Emily L Ricq, Emily T Graham, Vaishnavi V Phadnis, Pema Maretich, Sateja Paradkar, Natalie Boehnke, Amy A Deik, Ferenc Reinhardt, John K Eaton, Bryan Ferguson, Wenyu Wang, Joshua Fairman, Heather R Keys, Vlado Dančík, Clary B Clish, Paul A Clemons, Paula T Hammond, Laurie A Boyer, Robert A Weinberg, Stuart L Schreiber,

Ferroptosis-an iron-dependent, non-apoptotic cell death process-is involved in various degenerative diseases and represents a targetable susceptibility in certain cancers<sup>1</sup>. The ferroptosis-susceptible cell state can either pre-exist in cells that arise from certain lineages or be acquired during cell-state transitions<sup>2-5</sup>. However, precisely how susceptibility to ferroptosis is dynamically regulated remains poorly ... Read more >>

Nature (Nature)
[2020, 585(7826):603-608]

Cited: 34 times

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Syndecan-Mediated Ligation of ECM Proteins Triggers Proliferative Arrest of Disseminated Tumor Cells.

Tsukasa Shibue, Ferenc Reinhardt, Robert A Weinberg,

Systemic dissemination of tumor cells often begins long before the development of overt metastases, revealing the inefficient nature of the metastatic process. Thus, already at the time of initial clinical presentation, many patients with cancer harbor a myriad disseminated tumor cells (DTC) throughout the body, most of which are found ... Read more >>

Cancer Res (Cancer research)
[2019, 79(23):5944-5957]

Cited: 1 time

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Immuno-PET identifies the myeloid compartment as a key contributor to the outcome of the antitumor response under PD-1 blockade.

Mohammad Rashidian, Martin W LaFleur, Vincent L Verschoor, Anushka Dongre, Yun Zhang, Thao H Nguyen, Stephen Kolifrath, Amir R Aref, Christie J Lau, Cloud P Paweletz, Xia Bu, Gordon J Freeman, M Inmaculada Barrasa, Robert A Weinberg, Arlene H Sharpe, Hidde L Ploegh,

Immunotherapy using checkpoint-blocking antibodies against PD-1 has produced impressive results in a wide range of cancers. However, the response remains heterogeneous among patients. We used noninvasive immuno-positron emission tomography (PET), using <sup>89</sup>Zr-labeled PEGylated single-domain antibody fragments (nanobodies or VHHs), to explore the dynamics and distribution of intratumoral CD8<sup>+</sup> T cells ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2019, 116(34):16971-16980]

Cited: 32 times

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EMT and Cancer: More Than Meets the Eye.

Rik Derynck, Robert A Weinberg,

Epithelial cells acquire mesenchymal characteristics during development, wound healing and inflammation, and in cancer and fibrosis. With increasing appreciation of different roles of epithelial-mesenchymal transition (EMT), we address the question of how to define and recognize EMT processes and discuss their properties in cancer progression. ... Read more >>

Dev Cell (Developmental cell)
[2019, 49(3):313-316]

Cited: 60 times

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Acquisition of a hybrid E/M state is essential for tumorigenicity of basal breast cancer cells.

Cornelia Kröger, Alexander Afeyan, Jasmin Mraz, Elinor Ng Eaton, Ferenc Reinhardt, Yevgenia L Khodor, Prathapan Thiru, Brian Bierie, Xin Ye, Christopher B Burge, Robert A Weinberg,

Carcinoma cells residing in an intermediate phenotypic state along the epithelial-mesenchymal (E-M) spectrum are associated with malignant phenotypes, such as invasiveness, tumor-initiating ability, and metastatic dissemination. Using the recently described CD104+/CD44hi antigen marker combination, we isolated highly tumorigenic breast cancer cells residing stably-both in vitro and in vivo-in an intermediate ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2019, 116(15):7353-7362]

Cited: 99 times

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Epithelial-Mesenchymal Transition Induces Podocalyxin to Promote Extravasation via Ezrin Signaling.

Julia Fröse, Michelle B Chen, Katie E Hebron, Ferenc Reinhardt, Cynthia Hajal, Andries Zijlstra, Roger D Kamm, Robert A Weinberg,

The epithelial-mesenchymal transition (EMT) endows carcinoma cells with traits needed to complete many of the steps leading to metastasis formation, but its contributions specifically to the late step of extravasation remain understudied. We find that breast cancer cells that have undergone an EMT extravasate more efficiently from blood vessels both ... Read more >>

Cell Rep (Cell reports)
[2018, 24(4):962-972]

Cited: 21 times

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IL-1β inflammatory response driven by primary breast cancer prevents metastasis-initiating cell colonization.

Zafira Castaño, Beatriz P San Juan, Asaf Spiegel, Ayush Pant, Molly J DeCristo, Tyler Laszewski, Jessalyn M Ubellacker, Susanne R Janssen, Anushka Dongre, Ferenc Reinhardt, Ayana Henderson, Ana Garcia Del Rio, Ann M Gifford, Zachary T Herbert, John N Hutchinson, Robert A Weinberg, Christine L Chaffer, Sandra S McAllister,

Lack of insight into mechanisms governing breast cancer metastasis has precluded the development of curative therapies. Metastasis-initiating cancer cells (MICs) are uniquely equipped to establish metastases, causing recurrence and therapeutic resistance. Using various metastasis models, we discovered that certain primary tumours elicit a systemic inflammatory response involving interleukin-1β (IL-1β)-expressing innate ... Read more >>

Nat Cell Biol (Nature cell biology)
[2018, 20(9):1084-1097]

Cited: 48 times

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Epithelial-to-mesenchymal transition in cancer: complexity and opportunities.

Yun Zhang, Robert A Weinberg,

The cell-biological program termed the epithelial-to-mesenchymal transition (EMT) plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenchymal ... Read more >>

Front Med (Frontiers of medicine)
[2018, 12(4):361-373]

Cited: 105 times

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Understanding the tumor immune microenvironment (TIME) for effective therapy.

Mikhail Binnewies, Edward W Roberts, Kelly Kersten, Vincent Chan, Douglas F Fearon, Miriam Merad, Lisa M Coussens, Dmitry I Gabrilovich, Suzanne Ostrand-Rosenberg, Catherine C Hedrick, Robert H Vonderheide, Mikael J Pittet, Rakesh K Jain, Weiping Zou, T Kevin Howcroft, Elisa C Woodhouse, Robert A Weinberg, Matthew F Krummel,

The clinical successes in immunotherapy have been both astounding and at the same time unsatisfactory. Countless patients with varied tumor types have seen pronounced clinical response with immunotherapeutic intervention; however, many more patients have experienced minimal or no clinical benefit when provided the same treatment. As technology has advanced, so ... Read more >>

Nat Med (Nature medicine)
[2018, 24(5):541-550]

Cited: 727 times

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The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy.

Jordan A Krall, Ferenc Reinhardt, Oblaise A Mercury, Diwakar R Pattabiraman, Mary W Brooks, Michael Dougan, Arthur W Lambert, Brian Bierie, Hidde L Ploegh, Stephanie K Dougan, Robert A Weinberg,

Patients undergoing surgical resection of primary breast tumors confront a risk for metastatic recurrence that peaks sharply 12 to 18 months after surgery. The cause of early metastatic relapse in breast cancer has long been debated, with many ascribing these relapses to the natural progression of the disease. Others have ... Read more >>

Sci Transl Med (Science translational medicine)
[2018, 10(436):]

Cited: 94 times

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The SUMO guards for SNAIL.

Xin Ye, Robert A Weinberg,

Oncotarget (Oncotarget)
[2017, 8(58):97701-97702]

Cited: 4 times

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Upholding a role for EMT in breast cancer metastasis.

Xin Ye, Thomas Brabletz, Yibin Kang, Gregory D Longmore, M Angela Nieto, Ben Z Stanger, Jing Yang, Robert A Weinberg,

Nature (Nature)
[2017, 547(7661):E1-E3]

Cited: 116 times

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EMT programs promote basal mammary stem cell and tumor-initiating cell stemness by inducing primary ciliogenesis and Hedgehog signaling.

Vincent J Guen, Tony E Chavarria, Cornelia Kröger, Xin Ye, Robert A Weinberg, Jacqueline A Lees,

Tissue regeneration relies on adult stem cells (SCs) that possess the ability to self-renew and produce differentiating progeny. In an analogous manner, the development of certain carcinomas depends on a small subset of tumor cells, called "tumor-initiating cells" (TICs), with SC-like properties. Mammary SCs (MaSCs) reside in the basal compartment ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2017, 114(49):E10532-E10539]

Cited: 45 times

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Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells.

Mohammad Rashidian, Jessica R Ingram, Michael Dougan, Anushka Dongre, Katherine A Whang, Camille LeGall, Juan J Cragnolini, Brian Bierie, Monica Gostissa, James Gorman, Gijsbert M Grotenbreg, Atul Bhan, Robert A Weinberg, Hidde L Ploegh,

Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non-small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno-positron emission tomography (immuno-PET) can visualize tumors by detecting infiltrating ... Read more >>

J Exp Med (The Journal of experimental medicine)
[2017, 214(8):2243-2255]

Cited: 81 times

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Upholding a role for EMT in pancreatic cancer metastasis.

Nicole M Aiello, Thomas Brabletz, Yibin Kang, M Angela Nieto, Robert A Weinberg, Ben Z Stanger,

Nature (Nature)
[2017, 547(7661):E7-E8]

Cited: 102 times

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EMT, CSCs, and drug resistance: the mechanistic link and clinical implications.

Tsukasa Shibue, Robert A Weinberg,

The success of anticancer therapy is usually limited by the development of drug resistance. Such acquired resistance is driven, in part, by intratumoural heterogeneity - that is, the phenotypic diversity of cancer cells co-inhabiting a single tumour mass. The introduction of the cancer stem cell (CSC) concept, which posits the ... Read more >>

Nat Rev Clin Oncol (Nature reviews. Clinical oncology)
[2017, 14(10):611-629]

Cited: 668 times

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Emerging Biological Principles of Metastasis.

Arthur W Lambert, Diwakar R Pattabiraman, Robert A Weinberg,

Metastases account for the great majority of cancer-associated deaths, yet this complex process remains the least understood aspect of cancer biology. As the body of research concerning metastasis continues to grow at a rapid rate, the biological programs that underlie the dissemination and metastatic outgrowth of cancer cells are beginning ... Read more >>

Cell (Cell)
[2017, 168(4):670-691]

Cited: 755 times

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Integrin-β4 identifies cancer stem cell-enriched populations of partially mesenchymal carcinoma cells.

Brian Bierie, Sarah E Pierce, Cornelia Kroeger, Daniel G Stover, Diwakar R Pattabiraman, Prathapan Thiru, Joana Liu Donaher, Ferenc Reinhardt, Christine L Chaffer, Zuzana Keckesova, Robert A Weinberg,

Neoplastic cells within individual carcinomas often exhibit considerable phenotypic heterogeneity in their epithelial versus mesenchymal-like cell states. Because carcinoma cells with mesenchymal features are often more resistant to therapy and may serve as a source of relapse, we sought to determine whether such cells could be further stratified into functionally ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2017, 114(12):E2337-E2346]

Cited: 87 times

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Inflammation Triggers Zeb1-Dependent Escape from Tumor Latency.

Jasmine M De Cock, Tsukasa Shibue, Anushka Dongre, Zuzana Keckesova, Ferenc Reinhardt, Robert A Weinberg,

The emergence of metastatic disease in cancer patients many years or decades after initial successful treatment of primary tumors is well documented but poorly understood at the molecular level. Recent studies have begun exploring the cell-intrinsic programs, causing disseminated tumor cells to enter latency and the cellular signals in the ... Read more >>

Cancer Res (Cancer research)
[2016, 76(23):6778-6784]

Cited: 64 times

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Neutrophils Suppress Intraluminal NK Cell-Mediated Tumor Cell Clearance and Enhance Extravasation of Disseminated Carcinoma Cells.

Asaf Spiegel, Mary W Brooks, Samin Houshyar, Ferenc Reinhardt, Michele Ardolino, Evelyn Fessler, Michelle B Chen, Jordan A Krall, Jasmine DeCock, Ioannis K Zervantonakis, Alexandre Iannello, Yoshiko Iwamoto, Virna Cortez-Retamozo, Roger D Kamm, Mikael J Pittet, David H Raulet, Robert A Weinberg,

<h4>Unlabelled</h4>Immune cells promote the initial metastatic dissemination of carcinoma cells from primary tumors. In contrast to their well-studied functions in the initial stages of metastasis, the specific roles of immunocytes in facilitating progression through the critical later steps of the invasion-metastasis cascade remain poorly understood. Here, we define novel functions ... Read more >>

Cancer Discov (Cancer discovery)
[2016, 6(6):630-649]

Cited: 147 times

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Targeting the Epithelial-to-Mesenchymal Transition: The Case for Differentiation-Based Therapy.

Diwakar R Pattabiraman, Robert A Weinberg,

Although important strides have been made in targeted therapy for certain leukemias and subtypes of breast cancer, the standard of care for most carcinomas still involves chemotherapy, radiotherapy, surgery, or a combination of these. Two processes serve as obstacles to the successful treatment of carcinomas. First, a majority of deaths ... Read more >>

Cold Spring Harb Symp Quant Biol (Cold Spring Harbor symposia on quantitative biology)
[2016, 81:11-19]

Cited: 30 times

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Retraction Notice to: A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis.

Cell (Cell)
[2015, 161(2):417]

Cited: 3 times

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Distinct EMT programs control normal mammary stem cells and tumour-initiating cells.

Xin Ye, Wai Leong Tam, Tsukasa Shibue, Yasemin Kaygusuz, Ferenc Reinhardt, Elinor Ng Eaton, Robert A Weinberg,

Tumour-initiating cells (TICs) are responsible for metastatic dissemination and clinical relapse in a variety of cancers. Analogies between TICs and normal tissue stem cells have led to the proposal that activation of the normal stem-cell program within a tissue serves as the major mechanism for generating TICs. Supporting this notion, ... Read more >>

Nature (Nature)
[2015, 525(7568):256-260]

Cited: 334 times

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