“I don’t think we’ve ever been in a more exciting time in prostate cancer and oncology, with advances in targeted therapies, hormonal therapies, cellular therapies, radioligand therapies. We don’t know what’s the next big thing, but we know that all of those approaches can be refined even further. We’ve got the brightest minds in the world thinking about these challenges, and it’s our job to ensure that they have the funding to get their ideas into the clinic.”
“If you’re not an optimistic person and you choose a career in oncology, you’re probably not going into the right field,” says medical oncologist Charles (Chuck) Ryan, M.D., PCF’s new President and CEO.
No worries: Ryan is an optimist. “I’ve been an optimist my whole life.” In fact, he jokes, even his blood type is B positive! For the field of oncology in general, and prostate cancer specifically, there are many reasons to be optimistic, he continues: “There are patients in my clinic who are alive today because of the treatments we’ve developed in the last decade.”
Ryan, an internationally recognized clinician-scientist, has dedicated his career to helping men with advanced and recurrent prostate cancer. His research has focused on developing new hormonal and targeted therapies; new biomarkers to show the aggressiveness of disease and measure response to treatment; and also on survivorship issues facing men living with advanced prostate cancer. He has published more than 200 scholarly articles and textbook chapters, and is leader of the Advanced Prostate Cancer Cadre in the Alliance for Clinical Trials in Oncology, a national clinical trials group.
Ryan came to PCF from the University of Minnesota, where he was the B.J. Kennedy Chair in Clinical Medical Oncology, and where he served as Director of Hematology and Oncology and Associate Director of Clinical Research at the Masonic Cancer Center, an NCI-designated Comprehensive Cancer Center. He continues to see patients in Minneapolis: “I think being an active clinician makes me a better leader for PCF.”
TACTICAL Goal: New Therapies for Prostate Cancer
Ryan’s first major research initiative at PCF is a big one: a TACTICAL campaign (for Therapy ACceleration To Intercept CAncer Lethality) with one focus: overcoming treatment resistance in advanced prostate cancer – or, as Ryan puts it, addressing the factors that convert cancer into a disease that is lethal. “This is a specific call for people to develop new therapies. We are poised to fund several $5- to $10-million team science awards this year: we’re hoping to receive amazing ideas from the field,” from scientists who specialize in prostate cancer as well as scientists who don’t. Scientists who usually work on breast cancer, pancreatic cancer, and other cancers are welcome to bring their ideas to the table, too.
“Our hope is that this is the beginning of new therapies. I don’t think we’ve ever been in a more exciting time in prostate cancer and oncology, with advances in targeted therapies, hormonal therapies, cellular therapies, radioligand therapies. We don’t know what’s the next big thing, but we know that all of those approaches can be refined even further. We’ve got the brightest minds in the world thinking about these challenges, and it’s our job to ensure that they have the funding to get their ideas into the clinic.”
Changing the Prognosis
The field of cancer treatment has not always been so upbeat; in fact, until the 1980s, it was pretty depressing – because a diagnosis of cancer often meant a bleak prognosis. “Medical oncology didn’t even become a field until the early 1970s,” notes Ryan. “There was no fellowship, no board certifications.” When chemotherapy was developed to treat solid tumors, it was internists who began to administer these new, harsh drugs to patients. “My dad was one of those internists,” says Ryan. “He never trained in oncology, but he learned it on the fly as the field developed around him.”
Ryan’s father treated patients with many cancer types, “and I was proud of what he did. The problem is, not much of the treatment worked out all that well.” Ryan’s mom worked at the local hospice in his hometown of Appleton, Wisconsin. Ryan recalls sitting at the dinner table when he was growing up, hearing his parents talk about their work and “the breadth of misery that cancer could wreak on families and those who provided the care to them.” Unfortunately, many of his father’s patients with cancer “eventually became patients of my mother’s hospice team. That’s how it was in the 1980s: relatively little treatment to offer patients, good people doing their best to take care of them, poorly resourced clinical trials and structure, few active chemotherapies, and really nothing in terms of targeted treatments, immunotherapies, and the integration of tumor biology into treatment considerations.”
That began to change for prostate cancer patients in the early 1990s, thanks to philanthropist Michael Milken, founder of PCF. “CaPCure, now PCF, was formed by literally bringing together in the same room a small number of very bright minds: urologists, oncologists, and researchers.” At first, they met in Milken’s living room. “Many of those people have gone on to lead departments, cancer centers, and whole institutions. They helped launch PCF and became mentors to the next generation – my generation of researchers and clinicians.”
Throughout Ryan’s career – as a medical student and intern at the University of Wisconsin, as an oncology fellow at Memorial Sloan-Kettering Cancer Center, as a professor on the faculty at the University of California-San Francisco and then at the University of Minnesota – he has worked on PCF-funded projects. “This community, this family at PCF has really done some amazing things.” Because of PCF-funded research, “we’ve seen the average survival expectations for men with hormone-resistant prostate cancer extend from only about 11 months in the early 1990s to well over four years today,” with some exceptional responders living much longer. The treatment of men with metastatic prostate cancer has been transformed by therapies developed at PCF-funded labs and clinical trials, including: zoledronic acid, docetaxel, sipuleucel-T, denosumab, abiraterone, enzalutamide, radium-223, pembrolizumab, apalutamide, darolutamide, rucaparib, and olaparib.
“The Three P’s: Preserve, Prevent, and Prolong”
Talk to Ryan long enough, and he will tell you about “the three P’s.” These stand for Preserve, Prevent and Prolong; specifically: “preserving function, quality of life and activity level in advanced prostate cancer, preventing pain, hospitalizations and health decline, and prolonging life.” This seems like something everyone could get behind, right? Hospitals make these goals more oblique, he explains: “As an oncologist, when you order chemotherapy for a patient, you go into the electronic medical record,” and get asked certain automatically prompted questions, including: “’What is your goal of care with this patient when you’re ordering the chemo? Is it palliative or curative?’ Anybody who’s practiced oncology can see that the simplicity of that is irritating! Palliative means improving quality of life and symptoms, and is extremely important – but it’s not a dichotomy, not a binary choice between relieving symptoms and curing the cancer.”
What if, he continues, “every physician approached patients with the goal of the three P’s? That is going to lead to improved outcomes in men with prostate cancer, reduce deaths and suffering. There may be situations in which we can’t cure, but we can still preserve, prevent and prolong. Are we looking for cures? Of course! That is an unrelenting aspect of what we do at PCF. But there’s also a lot of good we can do for patients, even if we can’t cure them.”
Bringing the three Ps to PCF has the potential to affect many thousands of men: “This leads us to focus on things like survivorship, bone loss, muscle loss, cognitive impairment with ADT – issues of quality of life, even in situations where we can’t cure.”
An extension of this is Ryan’s goal for PCF to be a “global public square” for scientists, clinicians, patients and their families. “All are welcome,” he says. “Our community is global. We have funded research in 28 countries since our formation, and prostate cancer is a global disease, affecting 1.3 million men per year, and causing about 360,000 deaths per year – 35,000 in the U.S. alone last year.
“Scientists studying this disease, physicians treating patients, patients receiving therapy, patients cured of this disease, individuals who have family members with this disease and are worried they’re going to get it, spouses of patients who have this disease, or who have died of it – they all have a seat at our table.”
Very troubling to Ryan, and PCF, are new research findings showing the unevenness of care in the U.S. “It’s really striking,” he says. “Over the past couple of months, we have seen research showing that for men diagnosed with metastatic prostate cancer in the U.S. now, almost half are not getting the standard-of-care therapies. They’re getting treatments that are from a decade or 15 years ago! That’s something that is shocking to see. You can’t sit at PCF and feel like you are charged with reducing the death and suffering from prostate cancer and ignore statistics like that.”
That’s one fairly straightforward way to reduce deaths and suffering from prostate cancer. Ryan hopes the TACTICAL awards will be another. “If I didn’t think we had a lot of room to improve, I wouldn’t be the right person for this job.”