Publications by Douglas Hanahan

A new effLuc/Kate dual reporter allele for tumor imaging in mice

Douglas Hanahan, Ke Cheng, Elizabeth Anne Allen, Mélanie Louise Tichet

Genetically engineered mouse models (GEMMs) are instrumental for modelling local and systemic features of complex diseases, such as cancer. Non-invasive, longitudinal cell detection and monitoring in tumors, metastases and/or the micro-environment is param ...

The Company of Biologists2025

HPV16-Expressing Tumors Release Multiple IL-1 Ligands to Orchestrate Systemic Immunosuppression Whose Disruption Enables Efficacy of a Therapeutic Vaccine

Douglas Hanahan, Krisztian Homicsko, Jeremy Gilles Louis Guillot

It is well-established that symptomatic cancers evade immune destruction by coalescing tumor microenvironments to suppress adaptive immunity. Additionally, mouse models of cervical and other cancers have revealed a capability of tumors to systemically indu ...

American Association for Cancer Research (AACR)2025

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

Douglas Hanahan

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 ...

NATURE PORTFOLIO2024

Milestones in tumor vascularization and its therapeutic targeting

Douglas Hanahan, Michele De Palma

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 ...

Nature Portfolio2024

Embracing cancer complexity: Hallmarks of systemic disease

Johan Auwerx, Douglas Hanahan

The last 50 years have witnessed extraordinary developments in understanding mechanisms of carcinogenesis, synthesized as the hallmarks of cancer. Despite this logical framework, our understanding of the molecular basis of systemic manifestations and the u ...

Cell Press2024

Bispecific PD1-IL2v and anti-PD-L1 break tumor immunity resistance by enhancing stem-like tumor- reactive CD8+T cells and reprogramming macrophages

Douglas Hanahan, Krisztian Homicsko, Stephan Wullschleger, Mélanie Louise Tichet, Agnieszka Alicja Chryplewicz

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

CELL PRESS2023

Cancer hallmarks intersect with neuroscience in the tumor microenvironment

Douglas Hanahan

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 maligna ...

CELL PRESS2023

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

Douglas Hanahan, Stephan Wullschleger, Petra Catalina Schwalie, Mélanie Louise Tichet, Maria Karagianni

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 ...

NATURE PORTFOLIO2022

Aberrant hyperexpression of the RNA binding protein FMRP in tumors mediates immune evasion

Nadine Fournier, Douglas Hanahan, Krisztian Homicsko, Mohammad Sadegh Saghafinia, Dalya Ataca, Qiqun Zeng, Mélanie Louise Tichet, Yuqing Xie, Agnieszka Alicja Chryplewicz, Fleuriane Marie Tryskele Laurene Gallean, Jeremy Gilles Louis Guillot, Simge Yücel, Lucine Christe, Peng Zhang, Inti Zlobec

Many human cancers manifest the capability to circumvent attack by the adaptive immune system. In this work, we identified a component of immune evasion that involves frequent up-regulation of fragile X mental retardation protein (FMRP) in solid tumors. FM ...

American Association for the Advancement of Science2022

Cancer cell autophagy, reprogrammed macrophages, and remodeled vasculature in glioblastoma triggers tumor immunity

Julie Laetitia Scotton, Douglas Hanahan, Ksenya Shchors, Krisztian Homicsko, Mélanie Louise Tichet, Agnieszka Alicja Chryplewicz

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 re ...

2022

Reprogramming immunosuppressive tumor-associated macrophages potentiates standard-of-care therapy in melanoma

Douglas Hanahan, Mélanie Louise Tichet, Agnieszka Alicja Chryplewicz

AMER ASSOC CANCER RESEARCH2022

Co-targeting autophagy, macrophages and vasculature in glioma tumors triggers tumor immunity

Julie Laetitia Scotton, Douglas Hanahan, Mélanie Louise Tichet, Agnieszka Alicja Chryplewicz

AMER ASSOC CANCER RESEARCH2022

Hallmarks of Cancer: New Dimensions

Douglas Hanahan

The hallmarks of cancer conceptualization is a heuristic tool for distilling the vast complexity of cancer phenotypes and genotypes into a provisional set of underl y-ing principles. As knowledge of cancer mechanisms has progressed, other facets of the dis ...

AMER ASSOC CANCER RESEARCH2022

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

Douglas Hanahan

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 ...

2022

Cancer Cells Retrace a Stepwise Differentiation Program during Malignant Progression

Douglas Hanahan, Krisztian Homicsko, Stephan Wullschleger, Mohammad Sadegh Saghafinia, Iacovos Michael, Giovanni Ciriello

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 ...

AMER ASSOC CANCER RESEARCH2021

Co-targeting distinct hallmark capabilities for therapeutic benefit in pre-clinical GBM models

Douglas Hanahan, Agnieszka Alicja Chryplewicz

AMER ASSOC CANCER RESEARCH2021

The immunocytokine PD1-IL2v overcomes immune checkpoint resistance, and combination with an anti-PD-L1 antibody further enhances its anti-tumor activity

Douglas Hanahan, Stephan Wullschleger, Mélanie Louise Tichet

AMER ASSOC CANCER RESEARCH2021

Roadmap for the Emerging Field of Cancer Neuroscience

Douglas Hanahan, Xin Sun

Mounting evidence indicates that the nervous system plays a central role in cancer pathogenesis. In turn, cancers and cancer therapies can alter nervous system form and function. This Commentary seeks to describe the burgeoning field of "cancer neuroscienc ...

CELL PRESS2020

FMRP and cancer treatment

Douglas Hanahan, Qiqun Zeng

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 ...

2020

Myeloid Cells Orchestrate Systemic Immunosuppression, Impairing the Efficacy of Immunotherapy against HPV+ Cancers

Melody Swartz, Nadine Fournier, Douglas Hanahan, Stephan Wullschleger, Gabriele Galliverti, Mélanie Louise Tichet

Cancers induced by human papillomaviruses (HPV) should be responsive to immunotherapy by virtue of expressing the immunogenic oncoproteins E6/E7. However, advanced forms of cervical cancer, driven by HPV, are poorly responsive to immune response-enhancing ...

AMER ASSOC CANCER RESEARCH2020