Cancer

Cellular Pliancy and the Multistep Process of Tumorigenesis

Cell Cancer - 12 February 2018 - 12:00am
Completion of early stages of tumorigenesis relies on the dynamic interplay between the initiating oncogenic event and the cellular context. Here, we review recent findings indicating that each differentiation stage within a defined cellular lineage is associated with a unique susceptibility to malignant transformation when subjected to a specific oncogenic insult. This emerging notion, named cellular pliancy, provides a rationale for the short delay in the development of pediatric cancers of prenatal origin. It also highlights the critical role of cellular reprogramming in early steps of malignant transformation of adult differentiated cells and its impact on the natural history of tumorigenesis.
Categories: Cancer

Ezh2 and Runx1 Mutations Collaborate to Initiate Lympho-Myeloid Leukemia in Early Thymic Progenitors

Cell Cancer - 12 February 2018 - 12:00am
Booth et al. show that inactivation of Ezh2 and Runx1 in early thymic progenitors (ETPs) causes cell expansion and gene expression changes similar to those seen in human ETP leukemia. Addition of Flt3-ITD to the Ezh2−/−;Runx1−/− ETP cells leads to aggressive leukemia, which is sensitive to BET inhibition.
Categories: Cancer

Programming of Schwann Cells by Lats1/2-TAZ/YAP Signaling Drives Malignant Peripheral Nerve Sheath Tumorigenesis

Cell Cancer - 12 February 2018 - 12:00am
Wu et al. find that HIPPO-TAZ/YAP expression is elevated in malignant peripheral nerve sheath tumors (MPNST). Lats1/2 deficiency in Schwann cells induces hyperactivation of TAZ/YAP and increased PDGFR signaling, leading to the development of MPNST in mice. Inhibition of TAZ/YAP and PDGFR reduces MPNST growth.
Categories: Cancer

Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations

Cell Cancer - 12 February 2018 - 12:00am
Jeselsohn et al. show that estrogen receptor α (ER) mutations found in endocrine treatment-resistant metastatic breast cancers confer not only ligand-independent ER functions, but also allele-specific neomorphic properties. Importantly, the authors identify potential approaches for treating these breast cancers.
Categories: Cancer

The Integrated Genomic Landscape of Thymic Epithelial Tumors

Cell Cancer - 12 February 2018 - 12:00am
Radovich et al. perform multi-platform analyses of thymic epithelial tumors. They identify high prevalence of GTF2I mutations and enrichment of mutations in HRAS, NRAS, and TP53 and link overexpression of muscle autoantigens and increased aneuploidy in thymoma and patients' risk of having myasthenia gravis.
Categories: Cancer

Targeting the Senescence-Overriding Cooperative Activity of Structurally Unrelated H3K9 Demethylases in Melanoma

Cell Cancer - 12 February 2018 - 12:00am
Yu et al. show that two different types of histone H3 lysine 9 (H3K9) demethylases, LSD1 and JMJD2C, disable oncogenic Ras- or Braf-induced senescence by enabling the expression of E2F target genes, which permits transformation. Inhibition of the H3K9 demethylases restores senescence and controls tumor growth.
Categories: Cancer

Immunotherapy: Viral reprogramming

Nature Rev. Cancer - 9 February 2018 - 12:00am

Immunotherapy: Viral reprogramming

Immunotherapy: Viral reprogramming, Published online: 09 February 2018; doi:10.1038/nrc.2018.12

Two studies have shown that oncolytic virus treatment prior to surgery can prime the tumour immune microenvironment for subsequent immune checkpoint inhibition and lead to better outcomes in preclinical models of breast and brain cancers.
Categories: Cancer

Genetic insights into the morass of metastatic heterogeneity

Nature Rev. Cancer - 9 February 2018 - 12:00am

Genetic insights into the morass of metastatic heterogeneity

Genetic insights into the morass of metastatic heterogeneity, Published online: 09 February 2018; doi:10.1038/nrc.2017.126

In this Review, Hunter et al. discuss how genetic heterogeneity impacts metastatic disease and outline the implications of our current knowledge in this area for future research efforts and therapeutic interventions.
Categories: Cancer

From genetics to the clinic: a translational perspective on follicular lymphoma

Nature Rev. Cancer - 9 February 2018 - 12:00am

From genetics to the clinic: a translational perspective on follicular lymphoma

From genetics to the clinic: a translational perspective on follicular lymphoma, Published online: 09 February 2018; doi:10.1038/nrc.2017.127

This Review discusses the mutational landscape and evolution of follicular lymphoma. Deciphering the earliest initiating lesions and the molecular alterations leading to disease progression might help identify the most relevant targets for therapy of these tumours.
Categories: Cancer

RHOA G17V Induces T Follicular Helper Cell Specification and Promotes Lymphomagenesis

Cell Cancer - 1 February 2018 - 12:00am
Cortes et al. show that expression of Rhoa G17V in CD4+ T cells drives proliferation and Tfh polarization, and they develop an angioimmunoblastic T cell lymphoma model by combining Rhoa G17V expression and Tet2 loss. These tumors show increased ICOS and PI3K/MAPK signaling and are sensitive to pathway inhibition.
Categories: Cancer

Tumor Architecture and Notch Signaling Modulate Drug Response in Basal Cell Carcinoma

Cell Cancer - 30 January 2018 - 12:00am
Eberl et al. show that in mouse basal cell carcinoma models, interior Hh+/Notch+ suprabasal cells undergo apoptosis in response to vismodegib, whereas peripheral Hh+++/Notch− basal cells survive throughout treatment. Modulating Notch overcomes the drug response hierarchy established by tumor architecture.
Categories: Cancer

c-RAF Ablation Induces Regression of Advanced Kras/Trp53 Mutant Lung Adenocarcinomas by a Mechanism Independent of MAPK Signaling

Cell Cancer - 30 January 2018 - 12:00am
Sanclemente et al. generate oncogenic Kras mice that allow inducible deletion of Raf1, encoding c-RAF, and/or Braf in established KrasG12V or KrasG12V;Trp53−/− lung tumors. They show that systemic c-RAF ablation has limited toxicity and leads to significant tumor regression without having an impact on MAPK activity.
Categories: Cancer

Fanconi anaemia and cancer: an intricate relationship

Nature Rev. Cancer - 29 January 2018 - 12:00am

Fanconi anaemia and cancer: an intricate relationship

Fanconi anaemia and cancer: an intricate relationship, Published online: 29 January 2018; doi:10.1038/nrc.2017.116

Fanconi anaemia (FA) is a genetic disorder associated with bone marrow failure, congenital abnormalities and an increased risk of developing cancer. In this Review, Nalepa and Clapp describe the roles of FA proteins in maintaining genome homeostasis and explain how dysregulation of the FA pathway through mutations in the FA genes might lead to carcinogenesis.
Categories: Cancer

Tumour budding in colorectal cancer: molecular rationale for clinical translation

Nature Rev. Cancer - 29 January 2018 - 12:00am

Tumour budding in colorectal cancer: molecular rationale for clinical translation

Tumour budding in colorectal cancer: molecular rationale for clinical translation, Published online: 29 January 2018; doi:10.1038/nrc.2018.1

In this Comment, the authors outline the emerging rationale for the clinical use of tumour budding, a histological manifestation of tumour cell invasion, as a diagnostic tool and biomarker in colorectal cancer.
Categories: Cancer

Targeting minimal residual disease: a path to cure?

Nature Rev. Cancer - 29 January 2018 - 12:00am

Targeting minimal residual disease: a path to cure?

Targeting minimal residual disease: a path to cure?, Published online: 29 January 2018; doi:10.1038/nrc.2017.125

Improved therapies have allowed many patients with cancer to achieve complete remission, but they retain minimal residual disease (MRD), which causes relapse. This Opinion article argues that iterative detection, profiling and targeting of MRD could improve outcomes, including cure rates.
Categories: Cancer

Metabolism: Fusion power

Nature Rev. Cancer - 25 January 2018 - 12:00am

Metabolism: Fusion power

Metabolism: Fusion power, Published online: 25 January 2018; doi:10.1038/nrc.2018.2

The fusion gene consisting of fibroblast growth factor receptor 3 and transforming acidic coiled-coil-containing protein 3 is oncogenic and present in a small cancer subset. Frattini et al. have identified that this fusion gene drives peroxisomal and mitochondrial biogenesis.
Categories: Cancer

Tumour microenvironment: Radical changes

Nature Rev. Cancer - 25 January 2018 - 12:00am

Tumour microenvironment: Radical changes

Tumour microenvironment: Radical changes, Published online: 25 January 2018; doi:10.1038/nrc.2018.4

Reactive oxygen species derived from inflammatory myeloid cells is sufficient to induce mutagenesis in intestinal epithelial cells, independently of cytokines, to promote tumour initiation and progression.
Categories: Cancer

Tumour metabolism: The promoter becomes the suppressor

Nature Rev. Cancer - 25 January 2018 - 12:00am

Tumour metabolism: The promoter becomes the suppressor

Tumour metabolism: The promoter becomes the suppressor, Published online: 25 January 2018; doi:10.1038/nrc.2018.8

Tumour metabolism: The promoter becomes the suppressor
Categories: Cancer

Corrigendum: Ribosome biogenesis in cancer: new players and therapeutic avenues

Nature Rev. Cancer - 25 January 2018 - 12:00am

Corrigendum: Ribosome biogenesis in cancer: new players and therapeutic avenues

Corrigendum: Ribosome biogenesis in cancer: new players and therapeutic avenues, Published online: 25 January 2018; doi:10.1038/nrc.2018.3

Corrigendum: Ribosome biogenesis in cancer: new players and therapeutic avenues
Categories: Cancer

Oncogenes: Driving immune evasion

Nature Rev. Cancer - 25 January 2018 - 12:00am

Oncogenes: Driving immune evasion

Oncogenes: Driving immune evasion, Published online: 25 January 2018; doi:10.1038/nrc.2018.5

Three recent papers have shed light on how the common oncogenic drivers MYC and RAS can induce an immunosuppressive tumour microenvironment.
Categories: Cancer

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