Project acronym ImPRESS
Project Imaging Perfusion Restrictions from Extracellular Solid Stress
Researcher (PI) Kyrre Eeg Emblem
Host Institution (HI) OSLO UNIVERSITETSSYKEHUS HF
Call Details Starting Grant (StG), LS7, ERC-2017-STG
Summary Even the perfect cancer drug must reach its target to have an effect. The ImPRESS project main objective is to develop a novel imaging paradigm coined Restricted Perfusion Imaging (RPI) to reveal - for the first time in humans - vascular restrictions in solid cancers caused by mechanical solid stress, and use RPI to demonstrate that alleviating this force will repair the cancerous microenvironment and improve therapeutic response. Delivery of anti-cancer drugs to the tumor is critically dependent on a functional vascular bed. Developing biomarkers that can measure how mechanical forces in a solid tumor impair perfusion and promotes therapy resistance is essential for treatment of disease.
The ImPRESS project is based on the following observations; (I) pre-clinical work suggests that therapies targeting the tumor microenvironment and extracellular matrix may enhance drug delivery by decompressing tumor vessels; (II) results from animal models may not be transferable because compressive forces in human tumors in vivo can be many times higher; and (III) there are no available imaging technologies for medical diagnostics of solid stress in human cancers. Using RPI, ImPRESS will conduct a comprehensive series of innovative studies in brain cancer patients to answer three key questions: (Q1) Can we image vascular restrictions in human cancers and map how the vasculature changes with tumor growth or treatment? (Q2) Can we use medical engineering to image solid stress in vivo? (Q3) Can RPI show that matrix-depleting drugs improve patient response to conventional chemo- and radiation therapy as well as new targeted therapies?
The ImPRESS project holds a unique position to answer these questions by our unrivaled experience with advanced imaging of cancer patients. With successful delivery, ImPRESS will have a direct impact on patient treatment and establish an imaging paradigm that will pave the way for new scientific knowledge on how to revitalize cancer therapies.
Summary
Even the perfect cancer drug must reach its target to have an effect. The ImPRESS project main objective is to develop a novel imaging paradigm coined Restricted Perfusion Imaging (RPI) to reveal - for the first time in humans - vascular restrictions in solid cancers caused by mechanical solid stress, and use RPI to demonstrate that alleviating this force will repair the cancerous microenvironment and improve therapeutic response. Delivery of anti-cancer drugs to the tumor is critically dependent on a functional vascular bed. Developing biomarkers that can measure how mechanical forces in a solid tumor impair perfusion and promotes therapy resistance is essential for treatment of disease.
The ImPRESS project is based on the following observations; (I) pre-clinical work suggests that therapies targeting the tumor microenvironment and extracellular matrix may enhance drug delivery by decompressing tumor vessels; (II) results from animal models may not be transferable because compressive forces in human tumors in vivo can be many times higher; and (III) there are no available imaging technologies for medical diagnostics of solid stress in human cancers. Using RPI, ImPRESS will conduct a comprehensive series of innovative studies in brain cancer patients to answer three key questions: (Q1) Can we image vascular restrictions in human cancers and map how the vasculature changes with tumor growth or treatment? (Q2) Can we use medical engineering to image solid stress in vivo? (Q3) Can RPI show that matrix-depleting drugs improve patient response to conventional chemo- and radiation therapy as well as new targeted therapies?
The ImPRESS project holds a unique position to answer these questions by our unrivaled experience with advanced imaging of cancer patients. With successful delivery, ImPRESS will have a direct impact on patient treatment and establish an imaging paradigm that will pave the way for new scientific knowledge on how to revitalize cancer therapies.
Max ERC Funding
1 499 638 €
Duration
Start date: 2018-01-01, End date: 2022-12-31
Project acronym ProstOmics
Project 'Tissue is the issue': a multi-omics approach to improve prostate cancer diagnosis
Researcher (PI) May-Britt Tessem
Host Institution (HI) NORGES TEKNISK-NATURVITENSKAPELIGE UNIVERSITET NTNU
Call Details Starting Grant (StG), LS7, ERC-2017-STG
Summary Overtreatment in prostate cancer (PCa) is a burden for health care economy and for quality of life. Correct diagnosis of early stage PCa is challenging given the limitations of the currently available clinical tools and the biological understanding of PCa. In this inter-disciplinary project, I propose an innovative approach enabling several cutting-edge ‘omics’ technologies (spatial metabolomics, genomics, transcriptomics) as well as histopathology to be performed on the same tissue sample. My goal is to reveal the molecular mechanisms of novel, but also promising metabolite biomarkers (citrate, polyamines, succinate and zinc) and their connection to recurrence, tissue heterogeneity and immune responses in complex human tissues. Such markers can personalize PCa diagnosis, open up new treatment strategies and fundamentally change the view of how to analyze tissue samples in the future. Furthermore, I want to demonstrate that citrate and polyamines are reliable prognostic markers that can be analyzed both in tissue and in patients in vivo by MR spectroscopic imaging. This work is made possible by the availability of high-quality fresh frozen tissue biobanks of prostatectomy biopsies with 5-10 years of follow-up data (N=1000)/slices (N=1000) and targeted in vivo snap-shot biopsies from clinical MR guided procedures (N=100). Among other techniques, I will implement high speed MALDI imaging (RapifleX MALDI TissueTyper) to the multi-omics protocol to study the spatial distribution and provide high resolution metabolic maps for each cell type, and which can be matched to both histopathology and MR Imaging. Multi-disciplinary platforms on large cohorts are needed to explore the clinical potential of the suggested molecular mechanisms. I expect that this ambitious proposal will address the diagnostic challenges of PCa and will further inspire the clinic and scientific community to follow the multi-omics approach within diagnosis and cancer research.
Summary
Overtreatment in prostate cancer (PCa) is a burden for health care economy and for quality of life. Correct diagnosis of early stage PCa is challenging given the limitations of the currently available clinical tools and the biological understanding of PCa. In this inter-disciplinary project, I propose an innovative approach enabling several cutting-edge ‘omics’ technologies (spatial metabolomics, genomics, transcriptomics) as well as histopathology to be performed on the same tissue sample. My goal is to reveal the molecular mechanisms of novel, but also promising metabolite biomarkers (citrate, polyamines, succinate and zinc) and their connection to recurrence, tissue heterogeneity and immune responses in complex human tissues. Such markers can personalize PCa diagnosis, open up new treatment strategies and fundamentally change the view of how to analyze tissue samples in the future. Furthermore, I want to demonstrate that citrate and polyamines are reliable prognostic markers that can be analyzed both in tissue and in patients in vivo by MR spectroscopic imaging. This work is made possible by the availability of high-quality fresh frozen tissue biobanks of prostatectomy biopsies with 5-10 years of follow-up data (N=1000)/slices (N=1000) and targeted in vivo snap-shot biopsies from clinical MR guided procedures (N=100). Among other techniques, I will implement high speed MALDI imaging (RapifleX MALDI TissueTyper) to the multi-omics protocol to study the spatial distribution and provide high resolution metabolic maps for each cell type, and which can be matched to both histopathology and MR Imaging. Multi-disciplinary platforms on large cohorts are needed to explore the clinical potential of the suggested molecular mechanisms. I expect that this ambitious proposal will address the diagnostic challenges of PCa and will further inspire the clinic and scientific community to follow the multi-omics approach within diagnosis and cancer research.
Max ERC Funding
1 500 000 €
Duration
Start date: 2018-02-01, End date: 2023-01-31
