Operator of power tools by evenings and weekends; mad scientist by day. As the weeks passed—and as Steve Cosenza and his lovely wife, Debbie, continued dropping by to work on home and yard projects—I learned that Steve wasn’t just any ordinary mad scientist. He was a cancer researcher.
Which piqued my interest. Of course. Because Hubby was involved in a clinical trial a little more than a year ago. And although Hubby was dropped from the trial as cancer continued to spread, the trial itself—IMMU-132, a targeted therapy—has produced some good results.
With a B.A. in Biology from Rutgers University and a Ph.D. in Microbiology/Immunology from Temple University School of Medicine, Steve has numerous honors, awards, grants, publications and patents under his belt. When I asked about the most frustrating aspect of clinical trial work, he said that so many hours and weeks and months and sometimes years can be put into the work without making any headway:
This is not a job of instant gratification. What keeps you going are the times you walk into the lab and look at a result and BANG, it works just like you thought it would! Like running downhill – you are full of excitement and positive results drive you forward.
For patients considering a clinical trial, Steve suggests researching what’s available first—“A good website to look for trials is located at the NIH.gov site https://clinicaltrials.gov/“— and then asking at least two different oncologists from two different institutions or cancer centers. “This is for two reasons,” he says. “First, the oncologist will normally only suggest a trial that is being run at their hospital or center.” Which means there could be some bias. “Secondly, you want a hospital that is running lots of trials. That gives you more choices, but also normally means that this institution is on the cutting edge and looking at the newest treatment.” (See full interview with information about the different phases of clinical trials below.)
Steve tells a story about the most rewarding aspect of his work. “I was able to be part of a team of scientists and doctors who started developing a drug at our lab bench.” Ten years later, the compound was finally ready to treat patients. Steve tells about a seventy-year-old woman with terminal lung cancer who was their first patient. “She responded so well to our drug that she lived more than two years longer. She was able to spend so much more time with her family without the normal side effects that would have kept her from daily activities. There were a number of others, so no matter what happens to my career after this, I would say it has been worth all the years of effort!”
When Hubby was accepted into the IMMU-132 trial, it represented hope. Two weeks out of every three, Hubby boarded an early morning flight to Seattle, returning that same day, exhausted but in good spirits. And even if the trial didn’t end up working for him, it meant hope for someone. Many other someones. And Hubby was pleased that he could contribute in his own small way.
In the early 70s, there were 2-3 million cancer survivors in America. As of January 2014, there were 14.5 million survivors. Fourteen-point-five million people living well with and beyond cancer. Cancer is becoming more and more like a manageable chronic disease for many. And this is due to better education, better awareness around early detection, and particularly to cancer research leading to better treatments and less toxic side effects.
Steve Cosenza, Super Scientist and Power Tool Expert, says:
We as researchers/clinicians are indebted to the patients who decide to enter into clinical trials because without these trials, new drugs cannot be developed and approved.
No … thank you, Steve. We cancer patients and caregivers are indebted to you.
Mad Scientist Steve and his lovely wife, Debbie, with my Jersey grandkidlets
Full interview with Steve Cosenza, Senior Research Scientist at The Icahn School of Medicine at Mt. Sinai in New York City in the department of Oncological Sciences, and Pre-Clinical Drug Development Consultant for Onconova Therapeutics, New Jersey.
Was there a defining moment as a student that took you down the career path you chose? How did you happen into cancer research?
Steve Cosenza: I decided to take the basic science route at a small college in South Jersey. It is there that I really fell in love with research. At that time, I had one older professor in microbiology, and one young professor in developmental plant biology. They were complete opposites as far as their view on research as a career, but they both instilled a passion for investigating through research, new ideas and hypotheses. I loved reading about the complexity of cells, both mammalian and plants, especially in the area of growth and development. I was selected to enter into a research internship program at the Coriel Institute for Medical Research, and that is where I had my first taste of cancer research. It was exciting to see how scientists look at a problem, design experiments to test their hypothesis and then struggle through the process of running the experiments. Also how they use information we know—of how a cell, bacteria or virus works—and exploit this to use as an investigative tool. I was hooked from that point on!
What is your official title?
Steve Cosenza: My official title is Senior Research Scientist at The Icahn School of Medicine at Mt. Sinai in New York City, in the department of Oncological Sciences. I am also a Pre-clinical drug development consultant for a company called Onconova Therapeutics, NJ. This company was founded by my principle investigator, Dr. Premkumar Reddy. We have developed a number of targeted therapies for cancer, one of which is in phase III trials for Myelodysplastic Syndrome (MDS). This is a disease of the blood cells with many different abnormalities. We also have a program with the Department of Defense (DOD) for the development of a radiation protective agent for first responders.
What does a normal day at work look like?
Steve Cosenza: A typical day at the office, or in my case, the lab, can change on an instant or be rather structured for months, depending on how the experiments are working out. Each day is made up of looking at the previous results, analysis of data, looking through past literature, discussions with colleagues concerning the results and your analysis, then designing new experiments to ask the next question in the overall hypothesis. Then you work on the bench or in the tissue culture lab to run the experiments. This consists of preparing solutions, reactions, running gels, and growing and testing multiple types of cancer cells with our novel agents.
My lab is focused on screening a large number of compounds from the chemical library we have. If we find one that is selective for cancer cells we will also run additional experiments to look at mechanism of action (how/why the drug is killing cancer cells). If the compound still looks like a potential drug candidate, then I will run some initial animal experiments to look at toxicity, pharmacology (what are the characteristics of the compound in the blood and tissues of the animal), and finally efficacy studies (how well does the compound work in an animal model). We are also writing and submitting manuscripts and grant applications to fund our research.
Do you work closely with oncologists, or do you as a scientist come up with the “what if we tried this” scenarios?
Steve Cosenza: At this point, I have the opportunity to get feedback from the oncologists who are running the trials regarding specific patient populations that seem to be responding more significantly than others. They also have information on the patient genetic profile, in relationship to the disease, so we then do some in vitro/ in vivo (lab bench or animal) studies to determine if there are any biomarkers or genetic traits that we can link to responders. This information is very important to help select patients that will respond so that we do not waste their precious time on a treatment that will not work.
We get to publish our data together at meetings or publish articles together, so with certain oncologists, there is some active collaboration. Otherwise, once the drug is in the clinic, the doctors only share information with the company. The clinical trials, especially, phase I and II, can be modified during the trial depending on how the patients are responding, or the level of toxicities, etc., so there are always open discussions between the company folks (clinical oncologists, pharmacologists and researchers) and the oncologists.
What is the most frustrating aspect(s) of your work? The most rewarding?
Steve Cosenza: The most frustrating aspect of my work—and I tell this to all the students that I mentor—is that this is not a job of instant gratification. You can work hours, weeks, months and sometimes years, and never make any headway with your experiments. Most of the time you are dealing with technical issues, trying to create the reagents, cell lines, antibodies, etc., that you need just to run the first experiment to test your hypothesis, let alone, get a drug into the clinic. What keeps you going are the times you walk into the lab, look at a result and BANG, it works just like you thought it would! This leads you to take the next step. Like running downhill – you are full of excitement and positive results drive you forward.
The most amazing and blessed aspect of my job is that because I am involved in translational research (research that is from the bench to the clinic), I was able to be part of a team of scientists and doctors who started developing a drug at our lab bench. This compound was finally (10 years later) used to treat patients and we were able to see clinical benefits. Our first patient was a 70-year-old woman who was terminal with lung cancer. She was involved in our phase I trial and responded so well to our drug that she lived more than two years longer. She was able to spend so much more time with her family without the normal side effects that would have kept her from daily activities. There were a number of others, so no matter what happens to my career after this, I would say it has been worth all the years of effort! I was the first person ever to test our drug in cells and animals, which makes this program that much more personal for me.
You recently traveled to do a presentation. What was the presentation about? Who was the intended audience? Do you do presentations frequently?
Steve Cosenza: Yes, I attended and presented a poster at the 13th International MDS meeting. This is a relatively small meeting of clinicians, researchers, advocates and patients, so it was very focused on new trials and research targeted for MDS. I presented some very recent work on how rigosertib (this is our drug that is in clinical trials for MDS) is able to effectively kill acute myeloid leukemia (AML) cancer cells that are resistant to azacitidine.
Now, this is important because most, if not all, MDS patients also progress to AML and then the life expectancy is 3 months. At this point they have also failed azacitidine treatment, which is the standard of care of MDS and AML disease. In addition, we have shown that a subgroup of MDS patients who were refractory towards azacitidine treatment responded very well to rigosertib. We obtained two azacitidine resistant cell lines from a researcher in Japan and found that these cells were very sensitive to rigosertib, and we were able to show that treatment of these cells resulted in cell death, not just growth inhibition. In addition, we were able to observe that these cells, when treated with rigosertib first, became more sensitive towards azacitidine, which is called synergy. Therefore, this data has clinical relevance, and we are now further pursuing these studies.
This data was presented as a poster. Whoever was interested would stop by and I would walk them through the data and answer any questions. I personally do not attend too many meetings, however this is a very important part of our job – to exchange new data and get ideas from other researchers around the world. My boss and most of the oncologists go to many meetings throughout the year.
From your perspective, what would you say to cancer patients regarding clinical trials?
Steve Cosenza: The decision to enter into a clinical trial is a difficult one for many patients. They perceive this to be their last chance at survival. On the other hand, I have had patients tell me that they are excited to be part of the experimental process to determine if a new drug will help others. I have to say at this point, we as researchers/ clinicians are indebted to the patients who decide to enter into clinical trials because without these trials, new drugs cannot be developed and approved.
In my opinion, I would do as much research as I could before I entered into a clinical trial. There are many rules governing who can participate, so in most cases, only those who have no other choices can enter into a Phase I clinical trial. Phase I trials are typically dose limiting studies to determine the maximum tolerated dose that can be given without the patients experiencing severe toxicities or death. Some people will enter a Phase I at the lowest dose (beginning of the trial) and they will probably not get side effects, but the chances of the drug helping is low. Some may enter right at the end, so it could be toxic after the first dose. So I would wait for a certain trial until they are near the high end of dosing, and then ask the oncologist.
Phase II trials would be for patients who are running out of choices but are not without hope. These studies take the data from Phase I and expand the size of the study, or maybe combine two or three drugs. At this point, there is still not a lot of published data that the oncologist can look at to see responses from a larger number of patients, but there may have been some responses in the Phase I trial that they can use as a determining factor for their patient.
If there is a Phase III trial, there should be a lot of data available from past studies to see if you are a fit for this type of treatment. Even for the Phase II-III trials, entrance may be based on a number of criteria, such as the type of tumor, what genetic markers the tumor is expressing, etc.
I would ask at least two different oncologists from two different institutions or cancer centers. This is for two reasons; first, the oncologist will normally only suggest a trial that is being run at their hospital or center. (Each trial has to be approved at each individual institution.) Therefore, there is some bias for selection of the trial. Secondly, you want a hospital that is running lots of trials. That gives you more choices, but also normally means that this institution is on the cutting edge of the treatments and looking at the newest treatments.
Another aspect of trials is if it is double blinded with a placebo, standard care or open label. Most trials have to have a control, so you may not even be getting the experimental drug. These are all considerations a patient has to make. I would always stress that the patients should not let themselves get restricted by local hospitals. Go to where the treatment may be the best. Your family will understand if they cannot visit every day! A good website to look for trials is located at the NIH.gov site (https://clinicaltrials.gov/).