Publications

Furthering the prostate cancer screening debate (prostate cancer specific mortality and associated risks).

By:
Contributors: Bryan Donnelly, MD, MSc, FRCSC, Dean Ruether, MD FRCSC, Michael Chetner, MD, MSc, FRCSC, FACS, Peter Venner, MD, FRCPC
Can Urol Assoc J. 2011 Dec;5(6):416-21. doi: 10.5489/cuaj.11063.

Abstract

Screening for prostate cancer remains a contentious issue. As with other cancer screening programs, a key feature of the debate is verification of cancerspecific mortality reductions. Unfortunately the present evidence, two systematic reviews and six randomized controlled trials, have reported conflicting results. Furthermore, half of the studies are poor quality and the evidence is clouded by key weaknesses, including poor adherence to screening in the intervention arm or high rates of screening in the control arm. In high quality studies of prostate cancer screening (particularly prostatespecific antigen), in which actual compliance was anticipated in the study design, there is good evidence that prostate cancer mortality is reduced. The numbers needed to screen are at least as good as those of mammography for breast cancer and fecal occult blood testing for colorectal cancer. However, the risks associated with prostate cancer screening are considerable and must be weighed against the advantage of reduced cancerspecific mortality. Adverse events include 70% rate of false positives, important risks associated with prostate biopsy, and the serious consequences of prostate cancer treatment. The best evidence demonstrates prostate cancer screening will reduce prostate cancer mortality. It is time for the debate to move beyond this issue, and begin a well-informed discussion on the remaining complex issues associated with prostate cancer screening and appropriate management.

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 PubMed

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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