Matthew Dankner is a Medical Student at McGill University.
Matthew’s project has been generously supported by a gift from the Taite Boomer Foundation
Watch Matthew in a video sent February 2019: Developing Patient Derived Animal Models of Brain Metastasis
About the Research
Project title: “Using patient-derived xenograft models to identify mediators of brain metastasis in diverse cancers”
Brain metastasis occurs in over 11,000 Canadians per year and comes with a bleak prognosis for patients, with their mean survival being under 1 year. Little progress has been made in the development of successful treatments or biomarkers for brain metastasis in recent years. This is in part due to the artificial models and cell lines currently used to study brain metastasis, emphasizing the importance of establishing valid and clinically relevant patient derived xenograft (PDX) models of brain metastasis. This project aims to build and characterize a bank of PDX models of brain metastasis from breast cancer, lung cancer and melanoma using intra-cranial injections in immunocompromised mice. We hypothesize that our established bank of PDX models will be strongly similar to the surgically resected tissue and that it will reveal an expression signature common to all organ sites that can be modulated genetically and pharmacologically for application in functional experiments. This will allow us to employ the PDX models as powerful tools to study human brain metastasis, bringing us closer to developing therapeutics to treat this devastating complication of cancer.
About Matthew, in his own words…
Being awarded a Brain Tumour Research Studentship means that students like myself have the opportunity to join the rapidly growing field of brain tumour research in Canada. My work will be studying brain metastasis from solid tumours by establishing a number of patient derived xenograft animal models of the disease, something that has yet to be done in the field. These new animal models will allow us to explore the function of particular genes involved in brain metastasis, as well as test the efficacy of new drugs. I will ultimately use the clinical samples I obtain from the operating room to make new discoveries about the molecular mechanisms driving brain metastasis. This work hopes to directly improve the care of patients facing this devastating complication of cancer.
On my own behalf and that of my supervisors, Dr. Peter Siegel and Dr. Kevin Petrecca, I sincerely thank Brain Tumour Foundation of Canada, its donors, and the many patients who continue to donate their tumour samples for making this research possible. It is truly a privilege to work on this exciting research for the next two summers. I will do everything in my power to make a real difference in the field of brain metastasis with this award.
We have been successful thus far in generating a bank of patient derived xenografts of brain metastasis. As we obtain more patient samples, this bank will continue to grow and allow us to perform functional and pharmacological experiments exploring particular factors that we hypothesize to be pertinent in driving brain metastasis, as indicated by our future sequencing experiments as well as the in vitro blood-brain barrier screen. We have already begun exploring one of the patients from our bank in greater depth, and are excited by the potential outcome of these studies influencing the patient’s treatment. I strongly believe in the work outlined herein, and am certain that it will develop into a project that will impact both the research field, as well as patients suffering from brain metastasis. Read more…
Final Report – October 2017
My research project set out to create and characterize a large-scale repository of patient-derived xenograft models of brain metastasis. This means that human brain metastatic tissue was obtained directly from the neurosurgery operating room and injected directly into the brains of mouse hosts to grow new tumours that can be transferred indefinitely to more mice. The purpose of developing a large number of these models is to be able to study similarities and differences in the biology of brain metastases and to test new drugs intended to treat patients with brain metastasis.
Since initiating this work, we have developed a total of 22 patient-derived xenograft models that can reproducibly form brain tumours in mice (5 breast, 12 lung, 3 melanoma and 2 gastrointestinal primary site). Using these patient-derived mouse models, we have shown that a novel chemotherapy drug, is superior in treating breast cancer brain metastases compared to existing chemotherapies. In a separate project focused on melanoma brain metastases, we have observed that an already approved therapeutic regiment can benefit a new subset of melanoma brain metastasis patients. Both of these projects are currently being drafted into manuscripts to be submitted for publication, and are also being used as the basis for the development of rational human clinical trials for patients with brain metastases. In addition to completing these projects, the next step in this research hopes to perform genomic analysis of these brain metastasis samples to identify new genetic drivers that promote brain metastasis.
I am extremely thankful for the Brain Tumour Foundation Studentship. This award has allowed me to lay the groundwork for establishing this project and begin producing results that will be translated to the clinic in the form of clinical trials. This is particularly rewarding for me because as a future clinician-scientist, my overarching goal is to use findings from the laboratory to directly benefit patients. I certainly intend on continuing this work for the duration of my PhD and further in my career. I am extremely thankful to both Brain Tumour Foundation of Canada and the Taite Boomer Memorial Brain Tumor Foundation for funding and awarding this opportunity to me. I have, and will continue to, work my hardest each day to honour the generous investment they made in me to benefit patients with brain metastases.