Just a month ago, the transformation of two patients from inoperable prostate cancer to an operable condition to, now, cancer-free, had doctors hailing the dawn of a new era in which prostate cancer will change from a disease that is usually lethal to one that is usually curable.
“We have been looking for this for many years,” said Dr. Eugene Kwon.
Dr. Kwon, a senior investigator and urologist at the renowned Mayo Clinic in Minnesota, was amply justified in calling the latest findings on the drug ipilimumab the “Holy Grail of prostate cancer research.”
Both patients, part of a Phase II trial involving 108 patients, had late-stage cancer that had spread beyond the prostate to about “the size of a golf ball.” According to Dr. Kwon, “[Such patients] are usually offered only palliative care.”
The pair were given conventional drugs to remove the male hormones that fuel the growth of prostate cancer, followed by a single dose of an experimental drug, ipilimumab, a specially-engineered antibody that boosts the immune system’s ability to fight cancer.
The progress has been remarkably promising. So many cancer cells were killed off and the tumors had dramatically shrunk in size that both patients were able to undergo surgery. Following surgery, both have gone back to their normal lives.
Dr. Kwon has been working on the foundations of prostate cancer for over ten years, and this trial study, sponsored by the National Cancer Institute, the Department of Defense, and Richard M. Schulze Family Foundation, generated cautious optimism that this may be an enormous breakthrough that holds the first real promise for curing prostate cancer.
Dr. Kwon said, “We were startled to see responses that far exceeded any of our expectations.”
Dr. Kwon, as a kid, wanted to be a rock star. But he heeded his parents’ belief in education and encouragement to become a medical doctor. “My parents told me I have to be a doctor,” Dr. Kwon said playfully in a phone interview.
Prostate cancer parents all over the world may soon be grateful to Dr. Kwon’s parents.
Dr. Kwon explained he once stood at the crossroad of living a simple yet promising life or try to make an invaluable contribution to society that may not bear any fruition. In the end, he decided on the latter by declining a lucrative job offer from Beverly Hills, an affluent neighbor in California.
Dr. Kwon said he wanted to leave a legacy behind for the broader community. He joined the staff at National Institutes of Health for another 6 years of medical research.
“It was a very long extra level of training, but I wanted to change medicine. When someone’s put on this planet, one hopes to leave a legacy of favorable change behind for the next generation.”
And now, Dr. Kwon may have done just that, in a spectacular way.
KAP: Could you tell us more about your research?
Kwon: Historically, it’s been known since 1947 that prostate cancer is very sensitive to male hormone testosterone. Prostate cancer uses testosterone to grow and progress. It also has been recognized that if you remove testosterone or block it, the prostate cancer stops growing. But the effects of removing it are only temporary. For example, in an advanced stage, we would only expect temporary effects, from six months up to five years. Unfortunately, advanced prostate cancer is never curable. There are only temporary measures that can hold the prostate cancer back.
I worked with a famous immunologist, James P. Ellison, who discovered on and off switch for immune cells. This was the first off switch for immune cell called CTLA-4 receptor. He had the idea that if you block the off switch on immune cells, it would trigger an immune response more aggressively against the prostate cancer.
The question became how can we steer the response more against tumors specifically. If you leave it in the ‘on’ position, immune reaction would attack the normal parts of your body. Then I started thinking about how prostate cancer shrinks when testosterone is removed.
It was found that immune cells were flooding the prostate cancer. The prostate cancer was bruised by removing the hormone.
Many are trying to create a vaccine against the cancer, but by the time you take out the cancer and reengineer and put it back, by that time, you would end up with a small representation of what the immune system can recognize.
However, the manipulation of hormone uses entire tumors in their normal locations to vaccinate the body. This way we can vaccinate the patient using their own tumors to trigger their own reaction.
KAP: Was the intent of the study to cure prostate cancer?
Kwon: No, that was never the intent of the study. It was an accidental observation that was the byproduct of Phase II trial, which is the assessment of initially confirmed drug in a large group. Then, the study got shifted to begin to answer the question, ‘If you get such a big response, is it possible now to remove all of the cancer?’ At present, we still have 20 more patients we are waiting to see if they will also have a bigger response.
KAP: Are you planning a new clinical trial? If so, how soon?
Kwon: In the fall, we will be conducting a Phase II trial study on 30 men. Those 30 men will be all treated with hormone therapy and higher doses of ipilimumab repeatedly. If that study proves to be successful, then it would turn into a national Phase III study.
KAP: Could the experimental drug ipilimumab used for other types of cancer treatment?
Kwon: Well, these patients had also manifested losing their moles, legions on their skin, spontaneously. So, we concluded that the combination of hormone therapy and ipilimumab may trigger body-wide responses to go after other forms of hormone sensitive cancer, such as ovarian cancer.
As of this morning, I have received two hundred e-mails from Turkey, China, Hong Kong and elsewhere. I mean, there are so many people who need the cure, and that’s why we’re moving very quickly.
KAP: Do you tell your own kids to become a doctor?
Kwon: No. I just tell my daughter, 19, and son, 17, to get good grades. They don’t listen.
KAP: What is your ultimate goal?
Most cancer therapy has not advanced very dramatically, because there are very conservative ideas about how to manipulate it and attack it. My goal is to engineer entirely new approaches so that we can see dramatically improve responses treatment to cancer. Clearly, the current management of cancer will not be sustainable. It’s too expensive and too ineffective. Too many patients suffer and die.
We need some big findings now, and it won’t come from conventional wisdom. It requires extremely well engineered and scientifically sound, clever manipulation that have been explored before.
My goal is to try to come up with new therapies that would make a big impact on advanced cancer. Once we get to that point, at least I will feel better, because the reasons that I didn’t go into private practice was to make a contribution to society. Had I gone into practice, I would probably have been successful in the end. At the same time, I would have been following the instructions of everyone else and suffering with the various forms of therapy that are not effective. ♦
(C)보스턴캡 한인연합신문 KAP, The Korean American Press
