July 23, 2013
He is one of Canada’s foremost researchers, his work having impacted cancer research around the globe. While particularly acclaimed for his expertise in retinoblastoma protein, Dr. Fred Dick’s laboratory is focused on the fundamental mechanisms that regulate the mammalian cell division cycle and how they are disrupted in cancer. His publications and abstracts number more than 80 and he has been the recipient of numerous awards and accolades. However, this illustrious cancer researcher remains dedicated to his lab and students, acknowledging that the work is extremely challenging, but also highly rewarding.
Further proof of Dr. Dick’s high standing in the field of cancer research, he was recently invited to write an article on the state of knowledge of retinoblastoma protein function for the acclaimed journal Nature Reviews. Here, Dr. Dick takes time out of his busy schedule to talk about the review and answer some questions on his research.
Q. What is the retinoblastoma protein?
A. Proteins are like little nano machines that carry out specific functions in cells. The retinoblastoma (RB) protein plays a critical role in controlling cell division. Cancer is a disease of unwanted cell proliferation, so cancers always seem to find a way to prevent the RB protein from doing its job so that they can grow and spread. The name retinoblastoma is derived from a rare children's cancer. These patients succumb to this cancer because they inherit a bad copy of the RB gene. In the modern era we now understand that all cancers need to eliminate RB protein function. In some rare cases, such as the disease retinoblastoma, this is accomplished by destroying the gene that encodes the RB protein. Most cancers eliminate RB by altering its regulation so that it is constitutively turned off.
Q. How does RB work to prevent cancer?
A. This is the million dollar question. Blocking cell proliferation is the easy answer. The hard question is how. Our recent review seeks to capture the current state of our understanding of this question. In the review we outline how scientists generally think of RB from two different perspectives. One is that it has a single, central function that can be elicited in many scenarios that will block abnormal cell growth and keep us cancer free. The alternate view is that it is multifunctional and can undertake many biochemical tasks that depend extensively on the circumstances. Perhaps radiation makes it do one thing, and nutrient availability makes it do something else. The argument that we try to put forward in this review is that it is multi functional and that we now have sufficient data to say this based on a number of recent papers in the field published by a number of laboratories including mine.
Q. Why is RB function, and these recent findings, important to patients?
A. Cancer is a very diverse grouping of diseases. Based on the tissue of origin and the function of the cells that reside there, the properties of different cancers can vary widely. Not surprisingly, the manner in which they respond to treatment can vary considerably as well. Eliminating RB protein function appears to be a general requirement of all cancers, regardless of disease site. Perhaps because all cancers are characterized by unwanted cell proliferation, and RB is the master regulator of proliferation, this makes sense. It's important to emphasize that there are only a small number of regulatory pathways that appear to be broadly required in all cancers, regardless of disease site. Eliminating RB protein function is one of them. From this perspective understanding the RB protein's function has always been an intense focus of cancer researchers because understanding this pathway, and learning to manipulate it therapeutically, holds great promise for the clinic because it is critical to all cancers.
Q. What do you believe to be the next steps for RB research?
A. There are undoubtedly ways that we can utilize this new information about RB function to better fight cancer. I would say that the biggest challenge for the cell cycle and RB field now that we are confident in the multifunctional nature of this protein is to understand how all its different mechanisms of action relate to one another. If a cell encounters stress that causes DNA damage, does RB have a favourite way of responding? We know it can do many things, does it choose one first, or use a little of many functions at once. How does it decide this? So I would say that important work for the future is going to be formulating some sort of network logic that allows us to organize the RB protein's biochemical activities into a hierarchy. This will tell us how to manipulate it for therapeutic purposes and how to assess its functional state for predicting treatment response.
Dr. Fred Dick (Researcher at Lawson Health Research Institute and London Regional Cancer Program at LHSC) and his collaborator Dr. Seth Rubin (University of California, Santa Cruz) recently published the review: “Molecular mechanisms underlying RB protein function”. It can be found in the May 2013, Volume 14 edition of Nature Reviews: Molecular Cell Biology.