Movember Week 2 Interview With Dr. Michael Cox: Prostate Cancer

Michael E. Cox, Ph. D.

Associate Professor, Department of Urologic Sciences, University of British Columbia

Senior Scientist, The Vancouver Prostate Centre, Vancouver

Coastal Health Research Institute

Dr. Cox is a molecular and cellular biologist who earned his PhD in Biochemistry from the

University of North Carolina for studies on how cancer-causing genes normally function to

control nerve growth and differentiation. He began his work on cell signaling networks in cancer as a Research Associate at the University of Virginia. He has established a research program in Vancouver dedicated to understanding how prostate cancer, the most frequently diagnosed male malignancy, initiates and progresses and to finding ways of halting advanced disease progression.

1. What led you to pursue a career specifically dedicated to prostate cancer research?

I was working, actually looking at adrenaline release from adrenal chromaffin cells, cells of the adrenal gland that sit on top of the kidney, just the chromaffin cells, the cells in the middle not the cortical cells and I was looking at calcium clusters and how depolarization and calcium regulate intracellular kinase and while doing that we also had a project in the lab that was related to epidermal growth factors such as signalling and that did have a tie to breast cancer and I had developed abilities to map phosphorylation of proteins, and it involves using a lot of P32, and other basic techniques. I got called into that and had been working on that, we ended up doing some mapping on EGF receptor and brain cancer. I was at the University of Virginia associated with the cancer center and to apply the skills and the NIH put out a call for a program project related to prostate cancer and the team I was with there was pretty in-depth to program project and the fellow who was in charge of the cancer center at the time, he’s called Snuffy Myers. He got us together, he got some pilot money and said come up with some ideas and I put a couple of things together that came out of our EGF work but I was also interested in some stuff Snuffy had done related to neuro-endocrine because I had my Ph.D. and postdoctoral related to these neuro like cells. We started pursuing that and we were some of the first people to really describe the molecular details of what neuroendocrine transdifferentiation was in prostate cancer. And I was doing that again merely from a cellular basis and I wasn't thinking about patients at the time, I remember distinctly, I was a lab rat just doing my stuff I was really into biology and biochemistry and I really wasn't thinking about the patients. A friend of mine said I make cells "waah" I could do something to them to enable morphological change and I can characterize what those morphological changes were. There was a guy that used to go to the slaughterhouse and get the adrenal glands for us, you know a retired old guy and one day he couldn't go, turned out it was because he had prostate cancer advanced prostate cancer it was in metastasis in his bones and it was affecting his shoulders and bones and he passed away from the disease and I actually felt some regret because I’m working on the disease a little bit yet I’m just starting and I didn't even know the man, I didn't even know what was going and I felt a little bit of regret about that. I have a son who had a friend whose father developed prostate cancer and I didn't know the man he developed it very young and he didn't last long at all. I start thinking more and more about the disease perspective when I was looking for a position and the prostate center was recruiting me I was really quite interested in this because they had a component that I didn't see it in Virginia that ties directly to the clinic and so I was willing to come over here because I was gonna be able to work with clinicians and people who are working closer to it. So that's what got it started and then it just became dumb luck, get grants, get funded. You work on what you're funded to do. Try to maintain some integrity and I've been working in prostate cancer and that's become my niche.

2. How many people in North America are affected by prostate cancer?

Cancer now is the leading cause of death in North America and it has killed more people than any other single thing. About a third of people quarter to a third and amongst them the number one cause of cancer mortality is still lung cancer, it is declining, prostate cancer, colorectal cancer, breast cancer, and emerging as a lethal disease is pancreatic cancer, those are the next comers and major ones. Prostate cancer affects one in eight men. The US says they project 190 thousand diagnoses this year, in Canada, we project 23 thousand this year, so you're talking over 200 thousand, I don't know Mexico's numbers but they aren't going to be that much different. You're talking about 250 thousand males to be affected by prostate cancer this year alone. About 20% of that number dies. In Canada, we see 4 thousand deaths a year. Those are the stories that really affect me. You see a lot of guys diagnosed and it is a big impact, well in Canada we call it the 3rd leading cause of cancer-related deaths in men because colorectal and prostate cancer have swapped places. I think we will get a handle on colorectal in the short term. Lung cancer in men specifically because they aren't as exposed as they were back in the past. How many people? A lot. The other thing to keep in mind is prostate cancer is a disease that we do typically catch, whether from screening or symptoms; those things happen really regularly and have been working at this hard since 1990 or so. The research community has really been dedicated to coming up with treatments for prostate cancer for 20-30 years. Although the therapies that we used came out from the 60s. Men live a long time with prostate cancer, I think that's a huge burden that is really underrepresented and that's something Movember can do quite well and that's something that they wanna do. I have disagreements with people in different aspects of the research community about this, my affiliation with Movember and my willingness to talk to you guys is all because they are interested in survivorship and how to help men with the stresses of it all.

3. Who can be affected by this disease? Is there a specific demographic or group of people who are more susceptible to develop it?

We know that African Americans are more frequently diagnosed and with more aggressive diseases and have a higher mortality than Caucasians or Asians or Natives. It's hard to actually, this has especially been going on for a long time, and it's a tricky situation because we can talk about the little genetic differences that might exist and I told you about these translocations and has a different frequency, and that is inherent to the biology of men from different ethnicities. Demographics start to bring in all the environmental factors, and also brings in disparities in health care. Not sure how this will actually work out, there is a group in North America who are very active in trying to address the dexterity in the African American population. They really want us to not talk about the genetic undertones because they don't really think that they are there and well is too easy to catch "well... they got some mutation" that's too easy. We are not all that different and I'd like to see how it plays out. You also read things about how prostate cancer incidences are lower in Asia than in North America, but that is an awareness thing. There is plenty of prostate cancer in Japan. There are taboos around the disease, disease of "down there" and their culture keeps it under the radar. In other cultures where men live to be 78 years old and they don't even care and that's old age for them, it is just not tracked. Demographically the disease is more and more present but more frequently diagnosed in men who are old and so the older I get the less I like using that. The median age of diagnosis is 68. Men in their 50s or 40s can get diagnosed. The youngest I've seen a record off is in their 20s. But most men are old. That's almost all of them. Then what happens? A boy born today has a life expectancy of 85 years. Out towards what life expectancy is there are issues around how much worth people get for that. It is always easier to raise funds for children and so I think that we want to be able to deal with this and again the stigmas around disease related to sexual function get pushed aside. And you know men are supposed to be tough. Men don't speak up and talk about it.

4. What do you think downplays the significance of prostate cancer in today’s society, in the sense that it isn’t most people’s top priority or potential direct stress?

Things like breast cancer in women got a lot of attention, from a lot of people, worried about wives and mothers and daughters. It had an impact that was really acute, breast cancer is just a dangerous disease. We make parallels with breast cancer and prostate cancer, but they are very different. So that's how it started. It's back to men and supposed to be stoic and take it. A guy in his 70s gets cancer and how much money, how much money you going to spend on that guy, he is 70 years old and he's not going to make a fuss about it. If nobody makes a fuss about it you don't know what's happening. That is Movemebers moto, keep men healthy, and their whole mantra build from that issue. Men interact with the medical community differently than women do. Women are reproductive and engage with the medical community throughout their life, in their teens, in their 20s and when they are having kids, men just disappear, when was the last time you had a physical Roy? (Roy: When I was 18.). You haven't had one in over 2 years and most men don't. You know maybe for the better. Men in their 20-40s if think they are sick, they know they are sick, puncture your eardrum, you puncture your eardrum, it is what it is. But outside of that, there aren't a lot of reasons for me to go see a doctor unless you develop diabetes or other types of conditions. So you figure there isn't a point to burden the healthcare system for a yearly check-up to find nothing. How do you or when do you really re-engage men in the community? You try to do it when men are in their 40s, by then they still think they are impervious. And then start getting them into the medical system in their 50s, by that point blood pressure becomes an issue, cholesterol an issue, salt and diet, all of these problems that accumulate over time now start to come forth. My doctor looked at me when I tweaked my knee and asked when was the last time you got any blood work done, so he wrote up a prescription to get blood work done and that's it. They ask me, are you aware of prostate and colorectal cancer? They are worried about the things they can't see. In Canada, we have a community that is difficult to engage, the first nation community that we don't engage with, those guys are a bit of an issue. In BC, our outreach to the Chinese community is not as good as it could be the same with Indian and South Asian communities. We try to find ways to the point that at the foundation I work in two motorcyclists got into the Sikh community and their riders simply by riding with them. Heavily involved, as white as me. We have to rely on those guys to get into communities. We are not watching the same TV or radio so you have to find a way to get to those guys.

5. What are some ways prostate cancer can affect an individual’s lifestyle beyond the direct physical impacts of the disease and the treatment?

Curative intent therapy has dramatic impacts on urinary function such and various others and so those are the major impacts. The stress of the disease, guys are diagnosed with low-grade disease, we try not to intervene. The reason is that there is no evidence that treating now is more important than treating it a little bit. A guy diagnosed with a low volume of disease is likely to be advised to undergo active surveillance, monitor them once a year or every few months in order to see whether the disease is progressing and make a decision. The University of Toronto leads the world in this area and they are the world's experts off the charts and so that's happened a lot. With that comes the stress, so now these guys are anxious and they'll downplay it but they worry about it every day, and then their wife finds out about it and she's worried about it every day and there's a lot of anxiety and that becomes the biggest issue. Most guys will not be willing to talk about it, they don't want to get displaced and so they just keep quiet. So now there’s stress related to their employment, to their friends. They don’t want to get ostracized. If men actually do develop advanced disease, hormone therapy is the primary way we manage it, with a lot of side effects. Physical side effects are real, body changes. You feel exhausted, lethargic. They go through menopause and we aren't used to that. It is a slow decay. Our endocrinology changes differently than women.

6. From a professional standpoint and understanding of how the disease works, what advice can you give to those who may be dealing with it?

The whole thing, diagnosis, and stress, all that it’s just trauma. How do you deal with the fight or flight or freeze mechanism and the trauma is freeze, and so guys can get locked up. Join a club or whatever but there needs to be a way for men to express those issues and learn coping skills and mechanisms to go day to day with anxiety with breathing exercises, trying to calm down. Suiciadilyt is an issue for sure, I don't even pretend to work in that area, I'll happily moderate suicidality or mental health program in a few weeks. How do you get men to actually deal with what they keep inside and treat it with booze and stuff like that is not the answer.

7. If you don’t mind sharing, has there been a certain story that inspired you or continues to inspire you to keep pushing towards gaining a better understanding of such a deadly problem in your research?

I would hate to nail it to one person. Each person I've known that has been touched by a disease has been affected in a different way. Guys agree to be a part of trials and sign the paperwork off and they say I know this isn't going to help me, this is for my kids, my kid’s kids. These are the guys we want. I wouldn't say one, but I used snuffy as an example, he gave me a chance, he really got me into it, seeing how he manages has been really good. I have lost friends to the disease and I have friends who are battling the disease and they won't make it, they will die, how they are living with that knowledge is really empowering. These are guys who are willing to talk. I had a phone call with somebody and they were so negative, I could try and try and try but I got them to someone with a better commitment. There are just too many. They are all about grace and love. We all have to die right, people have said cancer is a good guy, you know you're going to die and you can deal with it. Die with a massive heart attack or stroke, you don't know.

8. After so many years of working in this field, what is one of the most important things you have learnt?

Prostate cancer I think is a manageable disease, we have a lot of really good therapies, many of them have consequential side effects, but the therapy is good and we are really good at it. So it would be very difficult to place those treatments, surgery or radiation, I don't see a change in that ever. The others we are moving around, be better at identifying specific guys with specific genetic events, take advantage of some of those, clinical trials are around bracket 1 and bracket 2. Approved drugs that are synthetically made that go after another DNA repair process. We see those types of treatments and we would screen guys. Well see those things move forward, we have hope in prostate cancer still, it's a cold disease but there are ways to crack it. People live, the biggest issue is survivorship. It's an important problem that is underappreciated, clinicians are very focused on doing what they do. They are treating that patient the best they can, and that's great, and they want all the funding in that type of research. A dim in that type of research so I would be cutting my nose but at the same time there is a huge population living with the disease and I think that's an important reality in 2021, we've got a huge population of men that's ever-growing and you guys are going to be dealing with this increase number of people older than you, it's coming and fits going to be on your hands. Getting at some biochemical molecular way at the earliest way of diagnosis is a very important step. We can identify guys who should or should not be treated better than before. There are always outliers on the distribution. How to segregate guys in the advanced stage as the disease evolves because it goes different directions to how to treat the disease towards different therapies or treat it and kill it in that state. If we can help them do better we can help as a society. Again this is a disease of old guys but we don't retire usually, people are still active, these are important members of society. If nothing less, they are the brain trust, these older guys, they are the resource we use to inform the next line or generation, you don't want to lose the knowledge. It's important that we help those guys and keep them engaged.

9. What are some steps men should take that will help with early detection of prostate cancer?

Early diagnosis is knowledge, what you do with that information is a different issue. Knowledge is power, if you know you can make a decision. Men should reach out to the medical community in their 50’s, they should get DREs (digital rectal exam), they should talk about family histories with breast and ovarian cancer because these family of diseases have common causes or familial relations. These are people that have in their families hereditary issues, being able to know that is important. A man gets diagnosed after his father died of prostate cancer. During genetic testing for the disease he has, it scores positive for specific inherited or evolved mutations. We now have the capacity to go and screen his kids. We are not at the point where full sequencing of everybody is a good idea, if they are not actionable we have added stress. Doing these genetics prospectively, letting the scientist not inform the patient of what they actually find in the full genome sequencing but working on it and trying to develop new ways to target it. That's how these trials work the best.

10. What are some ways outside of raising awareness, that people can help support the ongoing research of prostate cancer?

Talking about it is really important, getting out there and talking to your elder, father and uncles and make sure they know what's going on because they are probably not as informed as you. Convincing them that you care. Married men feel better than single men. Someone is looking after them. Awareness is important, increasing awareness is great, funding research is important too, disease-specific funding such as prostate cancer in Canada has taken a hit this year. Prostate Cancer Canada was our national cancer society for prostate research, that program went well for a decade, then ran into financial issues, so they were amalgamated into the Canadian Cancer Society. I know these people and I know they are committed to it and I work with them to this day. So I had sat on Prostate Cancer Canada’s research advisory council and then that amalgamation happened and I was really happy to reply yes when the executive director asked me to join the Canadian Cancer Society version of the same thing. The Candian Cancer Society is a great entity but it is interested in all cancers and so when that happened the support groups in the country, about 80, those guys have been tied to Prostate Cancer Canada and networking systems, it was abrupt and didn't see it coming and felt left out in the cold. Now that's not true, the guys who were a part of it made sure of communication, missteps were not on purpose that just happens. There is a real need to make sure that it works, can we develop another one that's like that, my foundation created the opportunity so that support groups across the country could get together. Silver Lining of zoom and the covid pandemic is everyone knows how to use Zoom. I got guys in their 80s running zoom on their iPad. We try to build a national support group program that has the capacity to across the country do awareness things on fathers day, September which is prostate cancer awareness month. To get people to be aware and to raise money. Movember is trying to do that this month and try to put money into programs but they have never done that before. Looking at survivorship and mental health issues. Major pharmaceutical investments in prostate cancer that are multinational, making sure those are happening and groups of leaders have it. Which drugs are covered by health and which are not, these are province to province. PSA testing has always been a watershed province, BC and Toronto don't cover it unless prescribed by a doctor. It's not expensive but it's the point of something that I have to pay for something that's $30. That gets in people's claws. Diagnosis of prostate cancer the way it presents is not cool, guys are likely to ignore, they creep up on you slowly. In support groups, they share everything, and they give and get support throughout their journey. In the support group, they find kindred spirits. Getting guys to engage and talk about it is important. They go home and want to forget about it.