Featured
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Article |
Systemic dysfunction and plasticity of the immune macroenvironment in cancer models
Primary tumor presence and progression shape the systemic immune landscape and immune responses to pathogens in multiple murine tumor models.
- Breanna M. Allen
- , Kamir J. Hiam
- & Matthew H. Spitzer
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Resource |
Multimodel preclinical platform predicts clinical response of melanoma to immunotherapy
Genetically engineered mouse models representing the spectrum of human cutaneous melanoma provide a platform for studying clinical responses to immunotherapy.
- Eva Pérez-Guijarro
- , Howard H. Yang
- & Glenn Merlino
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Resource |
A rectal cancer organoid platform to study individual responses to chemoradiation
Rectal cancer organoids retain the pathological features of matched patient tumors and recapitulate clinical responses to chemoradiation.
- Karuna Ganesh
- , Chao Wu
- & J. Joshua Smith
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Letter |
Inhibition of a G9a/DNMT network triggers immune-mediated bladder cancer regression
Inhibition of histone and DNA methyltransferase activity enhances sensitivity to platinum-based and immunotherapy in a novel transgenic mouse model of metastatic bladder cancer.
- Cristina Segovia
- , Edurne San José-Enériz
- & Jesús M. Paramio
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Resource |
The landscape of cancer cell line metabolism
Systematic metabolite profiling across cancer cell lines uncovers patterns associated with genetic and epigenetic features and reveals dysregulated metabolic states that can be exploited for anticancer therapy
- Haoxin Li
- , Shaoyang Ning
- & William R. Sellers
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Resource |
An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity
A biobank of ovarian cancer organoids recapitulates the histopathological and molecular hallmarks of patient tumors and provides a resource for preclinical research.
- Oded Kopper
- , Chris J. de Witte
- & Hans Clevers
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Resource |
A biobank of patient-derived pediatric brain tumor models
A resource of preclinical pediatric brain tumor models with detailed molecular characterization provides a platform for the community to test novel therapeutic approaches.
- Sebastian Brabetz
- , Sarah E. S. Leary
- & James M. Olson
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News & Views |
Modeling cytokine release syndrome
Complete leukemic responses to chimeric antigen receptor–modified T cells are invariably accompanied by severe toxicity. Recently developed animal models allow mechanistic dissection and prevention of toxicity without loss of therapeutic benefit.
- Cliona Rooney
- & Tim Sauer
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Letter |
Mutant KRAS-driven cancers depend on PTPN11/SHP2 phosphatase
The phosphatase SHP2 is required for mutant KRAS signaling in pancreatic and non-small-cell lung cancers and drives resistance to MEK inhibition.
- Dietrich A. Ruess
- , Guus J. Heynen
- & Hana Algül
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News & Views |
Organoids lead the cancer attack
In an article published recently in Nature Medicine, the authors generate organoid models of liver neoplasia. In doing so, they highlight both the diversity of current organoid methodologies and their application to cancer modeling and therapeutics discovery.
- Amber R Smith
- & Calvin J Kuo
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Article |
Human primary liver cancer–derived organoid cultures for disease modeling and drug screening
Tumor organoids derived from the most common subtypes of primary liver cancer recapitulate the histologic and molecular features of the tissues of origin, even after long-term culture. These in vitro models, as well as those for colorectal cancer reported in Crespo et al. in a previous issue, are amenable for drug screening and allow the identification of therapeutic approaches with potential for cancer treatment.
- Laura Broutier
- , Gianmarco Mastrogiovanni
- & Meritxell Huch
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Article |
A mouse model for embryonal tumors with multilayered rosettes uncovers the therapeutic potential of Sonic-hedgehog inhibitors
Simultaneous activation of Wnt and Shh pathways in murine neural precursor cells results in the formation of embryonal tumors with multilayered rosettes (ETMR) that recapitulate the histological and molecular features of human tumors. This novel mouse model represents a platform for evaluating therapeutic approaches for this rare malignant pediatric brain tumor, and provides novel insights into the cell of origin and molecular mechanisms driving the disease.
- Julia E Neumann
- , Annika K Wefers
- & Ulrich Schüller
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Article |
Combined mutation in Vhl, Trp53 and Rb1 causes clear cell renal cell carcinoma in mice
Through combined deletion of Vhl, Trp53 and Rb1 in renal epithelial cells, the authors develop a new mouse model of renal cell carcinoma that recapitulates the cellular and molecular features of a large proportion of human tumors. This model uncovers a role for primary-cilium-related genes in the development of the disease and provides a reliable platform for preclinical therapeutic studies.
- Sabine Harlander
- , Désirée Schönenberger
- & Ian J Frew
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Perspective |
Patient-derived induced pluripotent stem cells in cancer research and precision oncology
Cancer-derived induced pluripotent stem cells provide a new opportunity to model the effects of the cancer genome. In this Perspective, Eirini Papapetrou discusses the future applications of these cells for cancer modeling and therapeutic understanding.
- Eirini P Papapetrou
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Letter |
DNMT3A mutations promote anthracycline resistance in acute myeloid leukemia via impaired nucleosome remodeling
AML cells carrying R882 mutations in DNMT3A fail to sense and repair DNA damage induced by standard-dose chemotherapy as a result of impaired chromatin remodeling
- Olga A Guryanova
- , Kaitlyn Shank
- & Ross L Levine
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Technical Report |
Microenvironment-dependent growth of preneoplastic and malignant plasma cells in humanized mice
In a new mouse model of multiple myeloma, mice expressing the human versions of six proteins important for hematopoietic function were able to support the growth of primary human multiple myeloma xenografts, including both preneoplastic and malignant plasma cells.
- Rituparna Das
- , Till Strowig
- & Madhav V Dhodapkar
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Letter |
Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia
Cachexia-inducing tumors release complex factors that promote the increased uptake and burning of fats by muscle, resulting in muscle atrophy—a process that can be blocked if fatty acid oxidation is pharmacologically inhibited.
- Tomoya Fukawa
- , Benjamin Chua Yan-Jiang
- & Ng Shyh-Chang
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Article |
CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma
Expression of HNF1A and KRT81 stratifies pancreatic ductal adenocarcinoma tumors into different subtypes, and expression of cytochrome P450 3A5 mediates basal and/or drug-induced therapy resistance in each subtype.
- Elisa M Noll
- , Christian Eisen
- & Martin R Sprick
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Resource |
Evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers
Understanding tumor metastasis is crucial to developing more effective cancer therapies. Here McCreery et al. analyzed the mutational profile of metastases from chemically induced skin tumors in mice and found that parallel evolution of synchronously disseminated tumor cells underlies most metastasis.
- Melissa Q McCreery
- , Kyle D Halliwill
- & Allan Balmain
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Article |
High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response
The authors implement a collection of patient-derived xenograft tumors to test cancer drug responses.
- Hui Gao
- , Joshua M Korn
- & William R Sellers
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Letter |
Loss of BAP1 function leads to EZH2-dependent transformation
BAP1 regulation of EZH2 provides therapeutic opportunities in cancer.
- Lindsay M LaFave
- , Wendy Béguelin
- & Ross L Levine
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Article |
Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma
The bromodomain and extraterminal (BET) inhibitor JQ1 synergizes with the histone deacetylase inhibitor SAHA to suppress tumor growth in mouse models of pancreatic cancer.
- Pawel K Mazur
- , Alexander Herner
- & Jens T Siveke
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Article |
NY-ESO-1–specific TCR–engineered T cells mediate sustained antigen-specific antitumor effects in myeloma
Carl June and colleagues report the results of a phase I/II trial of adoptively transferred engineered T cells in patients with advanced multiple myeloma.
- Aaron P Rapoport
- , Edward A Stadtmauer
- & Carl H June
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Perspective |
Translational value of mouse models in oncology drug development
In this Perspective, Fred De Sauvage and Stephen Gould discuss the suitability of different mouse models for modeling cancer pathogenic processes, with an emphasis on applicability to developing cancer therapies.
- Stephen E Gould
- , Melissa R Junttila
- & Frederic J de Sauvage
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Technical Report |
A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer
The next generation of genetically engineered mouse models of pancreatic cancer involving a new inducible dual-recombinase system that combines Flp-FRT and Cre-loxP.
- Nina Schönhuber
- , Barbara Seidler
- & Dieter Saur
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Letter |
Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development
Elevated plasma levels of branched chain amino acids detected prior to pancreatic cancer diagnosis may result from whole body tissue breakdown occurring during the early stages of this disease.
- Jared R Mayers
- , Chen Wu
- & Brian M Wolpin
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Technical Report |
Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture
Modeling and documenting malignant progression in vitro without the need for in vivo transplantation represents a clear step forward for cancer investigation. Using an air-liquid interface methodology, Xingnan Li and colleagues show they can robustly model a range of gastrointestinal malignancies from pancreas, stomach and colon in primary epithelial/mesenchymal organoid culture. This setup is able to generate detailed histologic endpoints for oncogenic transformation in vitro and demonstrate in vivo tumorigenicity when the organoids are transplanted.
- Xingnan Li
- , Lincoln Nadauld
- & Calvin J Kuo
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Article |
Fas ligand–mediated immune surveillance by T cells is essential for the control of spontaneous B cell lymphomas
Immune surveillance has been proposed to eliminate transformed cells and thereby limit tumor formation. Axel Kallies and colleagues now report that spontaneous B cell lymphoma development in Blimp1-deficient or Bcl6-overexpressing mice is accelerated by T cell deficiency and identify the Fas-Fas ligand pathway as a crucial mediator of T cell control of lymphoma growth.
- Shoukat Afshar-Sterle
- , Dimitra Zotos
- & Axel Kallies
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News & Views |
A step toward functionally characterized prostate cancer molecular subtypes
ETS gene fusions and PTEN loss are common events in prostate cancer, but their interactions are not well understood. A new study in mice suggests that overexpression of ETS in the setting of PTEN loss increases androgen receptor binding and restores androgen receptor transcriptional activity (pages 1023–1029).
- Francesca Demichelis
- & Gerhardt Attard
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Resource |
Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes
By implementing the conditions for orthotopic implantation of different types of human breast tumors, the authors have created a publicly available bank of new mouse models that more faithfully recreate individual tumor properties and provide individualized information about tumor behavior and prognosis.
- Yoko S DeRose
- , Guoying Wang
- & Alana L Welm
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Technical Report |
Invasive three-dimensional organotypic neoplasia from multiple normal human epithelia
Deficiencies with current in vitro methods to assess cancer invasion prompted Todd Ridky and his colleagues to design a three-dimensional human organotypic epithelial cancer model using primary epithelial cells from multiple stratified epithelial tissues. The model recapitulates many of the features of tumor progression, including epithelial invasion through the intact basement membrane and supporting stroma. Studying epithelial tumor cell invasion in a more physiologic manner may help identify potential therapeutic targets for a range of epithelial tumors.
- Todd W Ridky
- , Jennifer M Chow
- & Paul A Khavari
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Between Bedside and Bench |
Finding the tumor copycat: Therapy fails, patients don't
The complexity of human metastatic cancer is difficult to mimic in mouse models. As a consequence, seemingly successful studies in murine models do not translate into success in late phases of clinical trials, pouring money, time and people's hope down the drain. In 'Bedside to Bench', Isaiah Fidler and Lee Ellis discuss crucial parameters in cancer growth and therapy and emphasize the disparity between studies in humans and mice. In 'Bench to Bedside', Terry Van Dyke shows how pancreatic tumors developed de novo in the organ site in mice can explain therapy failure in people with cancer and serve as a model to test new drugs.
- Lee M Ellis
- & Isaiah J Fidler
Cabozantinib for neurofibromatosis type 1–related plexiform neurofibromas: a phase 2 trial