Completed Projects

SFI - Science Foundation Ireland

Interrogating the in vivo antimetastatic action of LMWH tinzaparin and simvastatin in an orthotopic surgical resection mouse model of triple negative breast cancer: towards novel metastasis prevention strategies” SFI; Technology Innovation Development award; 2017-2018 ; €98,950 total award.

€110K allocated to Prof Byrne (Collaborator).


Two  million people die annually from cancer. Low-molecular-weight-heparin (LMWH) prolongs survival in cancer patients with long life-expectancy (early-stage disease) but not advanced malignancy. This suggests that LMWH prevents cancer death by inhibiting cancer-spread (metastasis). LMWHs inhibit metastasis in vivo but causes bleeding. Consequently, LMWH is unlikely to be used for preventing cancer-spread unless bleeding side-effects can be urgently addressed. In work supported by a previous SFI TIDA & recently published following patent application it has been demonstrated that LMWH-Tinzaparin enhanced endothelial-barrier function (which is crucial for preventing metastasis) & reduced tumour trans-endothelial-migration. Strikingly, the endothelial-protective cholesterol-lowering agent simvastatin greatly potentiated the effect of Tinzaparin, permitting endothelial-protection at a much lower concentration. If replicated in vivo, these findings could represent a novel therapeutic approach to inhibiting cancer spread, by delivering the metastasis-preventing properties of LMWH without exposing patients to a high bleeding-risk. There is a large addressable market for this invention & low predicted regulatory barriers: the invention combines existing drugs commonly prescribed in routine practice. The aim of this project is to provide further in vitro evidence and critically, in vivo proof-of-principle for the antimetastatic action of a LMWH/statin combination in a mouse model of breast cancer.

 

PI Prof . Annette Byrne 

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  • .SFI - Science Foundation Ireland
  • Improving the Efficacy of Bevacizumab in Glioblastoma; SFI; Technology Innovation Development award; 2015-2016; 129,646€ (total & allocated to Applicant) –
  • Patients diagnosed with the brain cancer Glioblastoma have a 14 month life expectancy. As Glioblastoma is a well vascularised tumour, targeting the disease with antiangiogenic drugs such as Bevacizumab (Avastin®)was thought to be a promising strategy that would lead to improved life expectancy. However, although the quality of life of Glioblastoma patients on Avastin is improved there is no increase in life expectancy. This is in part due to the mechanism by which Avastin may lead to increased invasion of the cancerous tissue into the surrounding brain. This project aims to develop a new drug, directly targeting the mechanism that Glioblastoma uses to invade the surrounding tissue. Our theory is that combining this drug with Avastin will increase the life expectancy of Glioblastoma patients.

PI Prof . Annette Byrne 

 

 

 

In ANGIOPREDICT, academic cancer biologists and industry-based biotechnology researchers will work together with clinicians to identify biomarkers to predict whether individual metastatic colorectal cancer patients will respond positively to Avastin® combination therapy. Diagnostic tests using these biomarkers will also be developed to provide clinicians with the means to predict patient treatment responses in the future.

https://www.angiopredict.com/

 

PI Prof . Annette Byrne 

 

Angio-Tox:

 

 

Inhibition of angiogenesis, the formation of new blood vessels from pre-existing vasculature, is a well established therapeutic strategy against cancer. Inhibitors of angiogenesis have been developed to block tumour growth and metastasis, and a number of these inhibitors are now clinically approved. However, contrary to initial expectations, angiogenesis inhibitors can cause a range of toxicities in patients.

AngioTox is a cross-sectoral collaboration in the field of biomedicine, responding to a pressing need to understand mechanisms of toxicity associated with angiogenesis inhibitor treatment. AngioTox is comprised of academic groups, SMEs, a global pharmaceutical leader in angiogenesis inhibitor development, and a large company concerned with monitoring drug modulation of cellular pathways. The goal of this consortium is to facilitate comprehensive histopathologic and mechanistic assessment of angiogenesis inhibitor related toxicities following treatment with the two main class of angiogenesis inhibitor; monoclonal antibodies and tyrosine kinase inhibitors. A combined in vivo modelling and digital histopathology approach will be engaged to comprehensively describe a new AngioTox Safety Panel of toxicologic markers. We will develop automated image analysis algorithms to enable quantification of morphological markers of angiogenesis inhibitor toxicity, and will undertake molecular profiling and ex-vivo studies to gain insight into mechanistic pathways. Specialized secondments proposed within AngioTox will facilitate several opportunities for high-end training of researchers across both industry and academia. Findings from the AngioTox programme may be directly utilised by academic, clinical and industry-based investigators to facilitate improved screening of angiogenesis inhibitor toxicologic parameters, inform clinical drug dosing regimens, facilitate the development of more specific and potent angiogenesis inhibitors, and significantly improve patient care.

PI Prof . Annette Byrne 

 

 

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