Translational Research

Translational Research

Translational research transforms scientific discoveries arising from fundamental studies into clinical applications to improve outcomes for patients with prostate cancer. Members of this team work together to employ innovative new technologies for biomarker discovery, detection and quantification that have been developed independently in internationally-recognized efforts in Alberta and bring them to bear on a common goal – developing better tests for prostate cancer.

The combination of prognostic biomarkers from distinct aspects of prostate cancer progression resulted in a test that is more sensitive, more accurate and more cost effective than current tests for prostate cancer.

Our overall goal is to improve patient outcomes and quality of life by translating novel tests to the clinic that are more sensitive, more accurate and more cost-effective than current tests for prostate cancer. No one dies from prostate cancer that is localized to the prostate – the spread, or metastasis, of prostate cancer is what makes it so dangerous. The five year survival rate for localized prostate cancer in North America is close to 100%, yet this drops to 30% for metastatic disease. The metastasis of prostate cancer is driven primarily by changes in growth factors, extracellular proteases, and the cell migration machinery. Biomarkers that are involved in these processes are prognostic for metastatic prostate cancer and their integration into a single powerful test are the focus of this multi-disciplinary team.

Our team is integrating internationally-recognized efforts in the characterization of tumour cell migration, growth factor signaling and protease-activated receptors to develop novel multiplex tests to more accurately predict outcomes in prostate cancer.

translational-research-image

Why did the chicken cross the road…?

Konstantin Stoletov and Lian Willetts co-first-authored an article published recently in Nature Communications titled “Quantitative in vivo whole genome motility screen reveals novel therapeutic targets to block cancer metastasis“. These two researchers, along with fellow Lewis lab members and collaborators from the University of Calgary and Vanderbilt University set out to determine what genes and signaling networks are involved in the rate-limiting steps of solid tumour cell motility, in vivo. But the team was hampered by the lack of an effective, quantitative, in vivo imaging platform. They wanted to visualize the movement of tumour cells, or lack of, in real-time AND use this intravital imaging platform to screen a large bank of tumour cells harboring single gene mutations for cells that show a loss of motility.

https://www.nature.com/articles/s41467-018-04743-2

When tumour cells metastasize they get into (intravasate) the hosts’ bloodstream and use the vascular system like roadways to travel throughout the body. This lets the tumour cells colonize new microenvironments where they will proliferate and form new tumours. So metastatis is really dependent on tumour cell motility. Although there are many different types of solid tumours known, previous research suggests that if the tumour cells can mobilize and metastasize then the expressed motility-related genes share homology across tumour types. This is great news because it would mean that therapeutic targets aimed at stopping motility could also stop metastasis for many tumour types!

Dr. Konstantin Stoletov

 

Dr. Lian Willetts
Dr. Lian Willetts

The Lewis lab researchers and their collaborators developed an in vivo, fluorescent, time-lapse screening platform that uses shell-less avian embryos for tumour growth and formation. The avian embryo is an excellent tumour model because the tumour cells will grow on the chorioallantoic membrane in a single cell layer, making in vivo cell motility imaging actually doable.

Using this platform the team screened over 30 000 human genes for the ones needed for cell motility and ultimately found 17 genes that looked to be effective metastasis-blocking gene targets. Stoletov, along with other Lewis lab members, are continuing this research by studying these 17 attractive candidates further to determine which one (s) would make therapeutic metastasis-blocking targets.

This article has generated a lot of interest in the scientific community and in the general public! Check out the links below to mentions and articles in the media.

https://www.biocentury.com/bc-innovations/translation-brief/2018-07-18/how-chicken-embryo-screen-identified-entos%E2%80%99-

https://www.ualberta.ca/medicine/news/2018/june/putting-the-brakes-on-metastatic-cancer

Stay tuned for a podcast that will be posted soon from “Parsing Science” where the hosts interview Dr. John Lewis about this work!

https://www.parsingscience.org/coming_soon/
UPDATE Oct 12, 2018: The podcast with John Lewis on Parsing Science called “Halting Cancers’ Spread“, is now available!

- Perrin Beatty