Publications de Douglas Hanahan

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Tumorigenesis embodies the formation of a heterotypic tumour microenvironment (TME) that, among its many functions, enables the evasion of T cell-mediated immune responses. Remarkably, most TME cell types, including cancer cells, fibroblasts, myeloid cells ...

We used the RIP1-Tag2 (RT2) mouse model of islet cell carcinogenesis to profile the transcriptome of pancreatic neuroendocrine tumors (PNET) that were either non-invasive or highly invasive, seeking to identify pro- and anti-invasive molecules. Expression ...

Pancreatic neuroendocrine tumors (PanNET) comprise two molecular subtypes, relatively benign islet tumors (IT) and invasive, metastasis-like primary (MLP) tumors. Until now, the origin of aggressive MLP tumors has been obscure. Herein, using multi-omics ap ...

A method for determining the prognosis for survival of a patient having cancer is disclosed, said cancer being altered (i.e. highly activated or alternatively inactive/inhibited) in the NMDAR signalling pathway, said method comprising determining the expre ...

Motivated by the recent implication of cysteine protease cathepsin L as a potential target for anti-cancer drug development, we used a conditional MycER(TAM); Bcl-x(L) model of pancreatic neuroendocrine tumorigenesis (PNET) to assess the role of cathepsin ...

Pancreatic neuroendocrine tumors (PanNETs) are a relatively rare but clinically challenging tumor type. In particular, high grade, poorly-differentiated PanNETs have the worst patient prognosis, and the underlying mechanisms of disease are poorly understoo ...

Despite their apparent success in pre-clinical trials, metalloproteinase (MMP) inhibitors proved to be inefficacious in clinical settings. In an effort to understand the underlying causes of this unanticipated outcome, we modeled the consequences of long-t ...

The cathepsin family of lysosomal proteases is increasingly being recognized for their altered expression in cancer and role in facilitating tumor progression. The aspartyl protease cathepsin E is overexpressed in several cancers and has been investigated ...

The present invention relates to methods and compositions which provide a companion diagnostic for cancer therapy. A method for identifying and stratifying a patient or group of patients with cancer as (i) being high or low for FMRP activity, (ii) having a ...

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 en ...

The associations of tricyclic antidepressants (TCAs) with reduced incidence of gliomas and elevated autophagy in glioma cells motivated investigation in mouse models of gliomagenesis. First, we established that imipramine, a TCA, increased autophagy and co ...

The present invention provides compositions and methods for down-modulating the expression and/or the immuno-suppressive activity of i) the FMRP protein, ii) an mRNA encoding the FMRP protein, and/or iii) the FMR1 gene for the treatment and/or prevention o ...

Research into the mechanisms and manifestations of solid tumor vascularization was launched more than 50 years ago with the proposition and experimental demonstrations that angiogenesis is instrumental for tumor growth and was, therefore, a promising thera ...

Recently we published two independent studies describing novel gene expression-based classifications of colorectal cancer (CRC). Notably, each study stratified CRC into a different number of subtypes: one reported 3 subtypes, whereas the second highlighted ...

Expansion and differentiation of antigen-experienced PD-1(+)TCF-1(+) stem-like CD8(+) T cells into effector cells is critical for the success of immunotherapies based on PD-1 blockade(1-4). Hashimoto et al. have shown that, in chronic infections, administr ...

Pancreatic ductal adenocarcinoma (PDA) is a lethal disease. Overall survival is typically 6 months from diagnosis(1). Numerous phase 3 trials of agents effective in other malignancies have failed to benefit unselected PDA populations, although patients do ...

Mutationally corrupted cancer (stem) cells are the driving force of tumor development and progression. Yet, these transformed cells cannot do it alone. Assemblages of ostensibly normal tissue and bone marrow-derived (stromal) cells are recruited to constit ...

Tumor-infiltrating macrophages typically promote angiogenesis while suppressing antitumoral T cell responses. In this issue of Cancer Cell, Klug and colleagues report that clinically-feasible, low-dose irradiation redirects macrophage differentiation from ...

Copper is an essential trace element, the imbalances of which are associated with various pathological conditions, including cancer, albeit via largely undefined molecular and cellular mechanisms. Here we provide evidence that levels of bioavailable copper ...

Purpose: Preclinical trials of a mouse model of pancreatic neuroendocrine tumors (PNET) were conducted to determine whether dual FGF/VEGF pathway inhibition with brivanib can improve first-line efficacy in comparison with VEGF inhibitors lacking fibroblast ...

Douglas Hanahan

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Convergent inducers and effectors of T cell paralysis in the tumour microenvironment

Genetic Deletion of the Desmosomal Component Desmoplakin Promotes Tumor Microinvasion in a Mouse Model of Pancreatic Neuroendocrine Carcinogenesis

Cancer Cells Retrace a Stepwise Differentiation Program during Malignant Progression

Method for determining cancer invasiveness and patient prognosis

Deficiency for the Cysteine Protease Cathepsin L Impairs Myc-Induced Tumorigenesis in a Mouse Model of Pancreatic Neuroendocrine Cancer

Identification and Characterization of Poorly Differentiated Invasive Carcinomas in a Mouse Model of Pancreatic Neuroendocrine Tumorigenesis

Increased invasiveness of MMP-9-deficient tumors in two mouse models of neuroendocrine tumorigenesis

Procathepsin E is highly abundant but minimally active in pancreatic ductal adenocarcinoma tumors

A pan-cancer classification based on fmrp pathway activity that informs differential prognosis and therapeutic responses

A set of microRNAs coordinately controls tumorigenesis, invasion, and metastasis

Dual Targeting of the Autophagic Regulatory Circuitry in Gliomas with Repurposed Drugs Elicits Cell-Lethal Autophagy and Therapeutic Benefit

FMRP and cancer treatment

Milestones in tumor vascularization and its therapeutic targeting

Reconciliation of classification systems defining molecular subtypes of colorectal cancer

PD-1-cis IL-2R agonism yields better effectors from stem-like CD8(+) T cells

Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy

Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment

A New Twist on Radiation Oncology: Low-Dose Irradiation Elicits Immunostimulatory Macrophages that Unlock Barriers to Tumor Immunotherapy

Bioavailable copper modulates oxidative phosphorylation and growth of tumors

Brivanib, a Dual FGF/VEGF Inhibitor, Is Active Both First and Second Line against Mouse Pancreatic Neuroendocrine Tumors Developing Adaptive/Evasive Resistance to VEGF Inhibition