So much to celebrate! From left: William Isaacs , Patrick Walsh with philanthropist Bernard Schwartz (seated). Schwartz has been a good friend to The Brady for many years: with his late wife, Irene, he established the Bernard L. Schwartz Distinguished Professorship in Urologic Oncology in 1996, once held by Alan Partin and currently held by H. Ballentine Carter. In 2000, Schwartz answered another call and established the Schwartz Research Fund to explore the role of dietary factors in the initiation and progression of prostate cancer, and when Walsh stepped down as Director of The Brady in 2004, Schwartz once again made a substantial gift to The Patrick C. Walsh Prostate Cancer Research Fund and became a member of our Founders’ Circle..
“Every year, worldwide, an estimated 1,111,700 men are diagnosed with prostate cancer and 307,500 men die from it,” says William Isaacs, Ph.D., the William Thomas Gerrard, Mario Anthony Duhon and Jennifer and John Chalsty Professor of Urology. “The wide discrepancy between these two numbers shows that only a subset of these cancers progress to lethal disease.” This is good news for most men with prostate cancer – but men who have, or are at risk of getting, aggressive prostate cancer are desperately in need of smarter diagnosis and more specific treatment.
The key to more precise treatment for aggressive prostate cancer is in understanding the genes of that man’s specific cancer. Some drugs work much more effectively against particular mutated genes when cancer has escaped the prostate. Even when cancer is caught in the early stages, it’s critical to understand a man’s genetic risk – whether his cancer is aggressive or more benign.
A mutated version of the HOXB13 gene, discovered by Isaacs and his team, is the first verified prostate cancer susceptibility gene. Isaacs and colleagues at other centers have also discovered that more commonly mutated genes – defects that can cause several different types of cancer – are major factors in inherited prostate cancer risk, as well. For example, “work from our lab and others has shown that BRCA2 mutations increase the risk not only for prostate cancer, but for an aggressive form,” says Isaacs. In fact, “we now know that about one in 10 men who die from prostate cancer carry a damaged copy of BRCA2 or another gene involved in DNA repair, such as ATM.”
Finding one of these mutations in a man with prostate cancer has implications for his family, as well: “each child has a one-out-of-two chance of inheriting the risky gene. How many more BRCA2-like genes can predict aggressive disease risk and drug sensitivity?” Isaacs wonders. “So far, the list of these genes is quite short.”
As part of The Patrick C. Walsh Hereditary Prostate Cancer Program , “in an effort to find additional genes that can predict prostate cancer risk, we have begun a large study, sequencing each of the over 20,000 inherited genes from different sets of prostate cancer patients: men with highly aggressive or lethal disease, men with more indolent or benign disease, and men with multiple affected family members.”
So far, Isaacs and his team have found a number of candidate susceptibility genes: mutated genes that are more common in men with aggressive disease than in men with low-risk disease, and are present in multiple members of prostate cancer families. “We are in the process of testing these candidates now,” says Isaacs. “So far, at least one gene has emerged that is worthy of further study: a gene called PPFIBP2, which also has been implicated in metastatic breast cancer. “They have found mutations in this gene more often in men with aggressive prostate cancer than in men either with less-aggressive disease, or men who don’t have prostate cancer. Also,“we have observed multiple families where each affected member carries the same mutation in this gene.”
Much more work is needed, Isaacs notes. One day, he hopes, the presence or absence of such genes “will guide our treatment decisions, so that every man is treated appropriately for his specific prostate cancer risk.”
On February 13, 2018, Patrick C. Walsh, M.D., University Distinguished Service Professor Emeritus, and Director of The Brady for three decades, turned 80. The Brady wished to honor this milestone, and asked Walsh for his suggestions. He recommended that we contact his former patients, asking for their help in completing the work he began in the 1980s with molecular biologist William Isaacs, Ph.D., the William Thomas Gerrard, Mario Anthony Duhon and Jennifer and John Chalsty Professor of Urology.
Walsh’s scientific passion is hereditary prostate cancer research. In fact, he and Isaacs were the first to identify and define hereditary prostate cancer, and to discover that prostate cancer is one of the most “heritable” cancers: inherited genetic factors play a role in about half of all men with prostate cancer, and inherited faulty genes account for at least 10 to 15 percent of deaths from this disease.
“In honor of his 80th birthday, we wanted to recognize Pat Walsh with a gift that would bring him great pleasure and fulfillment. Through the generosity of many of his friends and longtime patients, we have established The Patrick C. Walsh Hereditary Prostate Cancer Program, to determine the genetic causes of, and develop effective treatments for, hereditary prostate cancer,” says Alan W. Partin, M.D., Ph.D., The Jakurski Family Director and Professor.
The Brady is uniquely poised to carry out this mission, Partin adds: “Over the past 30 years, with Dr. Walsh’s leadership, we have built one of the world’s largest collections of hereditary prostate cancer samples, with more than 3,000 families and 8,000 individual patients, available for sequencing studies. With funding, we will use advanced DNA sequencing technologies to find the genes responsible for the strong hereditary predisposition to the disease.”
Already, with generous support from more than 125 donors from the U.S. and several other countries, this project is under way and sequencing has begun. The first major contribution came from Bernard Schwartz, a longtime supporter of The Brady and member of our Founder’s Circle.
There’s even more to come: The Brady plans to raise funds to start a Hereditary Prostate Cancer clinic, to be run by urologist Christian Pavlovich, M.D. This will include a comprehensive genetic testing and counseling program to test men for mutations in important genes related to prostate cancer: HOXB13, as well as DNA-repair genes such as BRCA1, BRCA2, ATM, and the others that we expect to discover as a result of the current sequencing efforts.
For the first time, we have the potential to identify every gene involved in hereditary prostate cancer. This history-making project will help thousands of men and their families to understand their family cancer risk, seek early detection and treatment, and save many lives.
Each year, more than 160,000 American men are diagnosed with prostate cancer. The good news is that more men are being cured of this disease than ever before.
Now in a revised fourth edition, this lifesaving guide – Amazon’s #1 Bestseller in Men’s Health for 24 years – by renowned expert Dr. Patrick Walsh and acclaimed science writer Janet Farrar Worthington offers a message of hope to every man facing this illness. Prostate cancer is a different disease in every man—which means that the right treatment varies for each man. Giving you a second opinion from the world’s top experts in surgery, pathology, urology, and radiation and medical oncology, this book helps you determine the best plan for you. Learn:
Discovery is published by
THE JAMES BUCHANAN BRADY UROLOGICAL INSTITUTE
Johns Hopkins Medicine
600 North Wolfe Street, CMSC 130
Baltimore, Maryland 21287-2101
410.955.8434 | urology.jhu.edu
Patrick Walsh, M.D. University Distinguished Service
Professor of Urology Emeritus
Janet Farrar Worthington Writer/Editor
Laura LeBrun Hatcher Design & Art Direction
Keith Weller Principal Photography
Our research is evolving. Today, we are curing urological cancers that were not curable even a few years ago, with better diagnosis, refined surgery and radiation, and newly discovered classes and combinations of drugs. Through the incredible generosity of our patients and friends, our world-class scientists are leading an all-out effort to track down the genes involved in hereditary prostate cancer. We’re also looking at the genes of men who ar e considering Active Surveillance, to make sure this is a safe option for them, and w e are finding genetic and molecular markers that can tell us which men with the most aggressive prostate cancer can benefit from immunotherapy.
Our scientists at the Greenberg Bladder Cancer Institute continue to lead the field with pioneering molecular subtyping of cancer — finding specific gr oups of people with similar types of cancer, who will respond better to particular treatments — with new immunotherapy and chemotherapy approaches, and innovative mini-bladders, made from a patient’s own cells. In renal cancer, our strategy of highly patient-specific treatment has allowed hundreds of people to be safely monitored for small tumors, and our multidisciplinary “Go Team” is saving the lives of people who have tumors that are considered inoperable at other centers. Finally, with great sadness but also much joy, we honor the life of our beloved research director and friend, Donald S. Coffey, whose legacy continues in the generations of scientists he has trained.
Alan W. Partin, M.D., Ph.D.
The Jakurski Family Director
Professor of Urology
The James Buchanan Brady Urological Institute
The Brady lost a good friend last year, and the international world of prostate cancer research lost one of its brightest stars, a brilliant scientist, scholar, thinker, mentor and teacher.
For more than half a century, Donald S. Coffey, Ph.D., made The Brady a better place just by being here; for 30 of those years, he was our Director of Research – a scientific legend who trained and inspired generations of fellows and students and was a powerful driving force in the careers of dozens of scientists who were trying to understand prostate cancer. A gifted storyteller, he not only ignited the imagination and creativity of his students and colleagues; he genuinely cared about them. He was remarkable for his quick mind and gift for cutting through even the most intimidating scientific challenges to find the simple questions at the heart of them.
“Don was a genius,” says longtime friend and colleague, Patrick C. Walsh, M.D., Distinguished Service Professor Emeritus. He credits Coffey’s “brilliant ability to simplify” as the key factor in one of Coffey’s most important discoveries, the nuclear matrix of cells, the scaffolding that provides the structure of a cell’s nucleus, and helps organize its DNA. In cancer cells, Coffey discovered, the nucleus looks different. “As a non-pathologist,” explains Walsh, “he was able to simplify the pathology of cancer down to one rule: The nucleus is irregular. He then set out to find what makes a nucleus round, and in the process, discovered the nuclear matrix.”
But of all of Coffey’s achievements, the most important is that he has attracted, inspired, and trained the leaders in the field. “He is truly the father of modern science in prostate disease because of the many scientists he has personally trained, and the hundreds of others he has influenced,” says Walsh. “Today, when one looks at the leaders in urological research, every one of them has the imprint of Don Coffey, one way or another.”
Don Coffey: Brilliant scientist, storyteller, mentor, and friend.
Alan W. Partin, M.D., Ph.D., didn’t know he wanted to be a urologist until he spent four years working in Coffey’s lab as a graduate student; before that, he had wanted to be a pediatrician. “Don Coffey had the most unique grasp of human nature I have ever witnessed,” says Partin. “He touched the lives of countless individuals both within urology and oncology, and pressed them always to ask the question, if this is true, what does it mean?”
Coffey’s approach to teaching was simple. “Tell me the smartest people, and I don’t care what they do, I’m helping them.” A partial list of his former graduate students includes some of the top scientists in urology and oncology: Alan Partin, William Nelson, Ken Pienta, Ballentine Carter, Drew Pardoll, Arthur Burnett, Bert Vogelstein, John Isaacs, Herb Lepor, Angelo De Marzo, Shawn Lupold, William Isaacs, Andrew Fineberg, Alan Meeker, Lelund Chung, Warren Heston, and Jonathan Simons. “All these great people,” said Coffey. “It’s not that I teach them anything. It’s that, if you’re the best, I’ll give you an opportunity to do your thing, and we’re on our way.”
Among many other honors and awards, Don Coffey served as President of the American Association for Cancer Research, the largest cancer research society, with 35,000 members from 110 countries. He was President of the Society for Basic Urologic Research, and served on several major editorial boards. For 19 years, he served as a member of the National Prostatic Cancer Program of the National Cancer Institute, and as National Chairman of this board for four years. He published more than 250 research papers. Coffey received the Robert Edwards Award from the Tenovus Institute, both the Fuller Award and the Lifetime Achievement Award from the American Urological Association, the First Society of International Urology- Yamanouchi Research Award, that society’s highest research award, and the Distinguished Service Award from the American Cancer Society.
In 2015, Coffey received the American Association for Cancer Research’s highest honor, the Margaret Foti Award for Leadership and Extraordinary Achievements in Cancer Research. He was the recipient of two Merit Awards from the National Institutes of Health.
Said Coffey about his work: “I’ve dedicated my life; I hope to die doing this. I don’t need any more honors, I’m paid more than I’m worth, I probably should get out of the way, but I still have questions.”
Partnerships with donors make discoveries possible. Thank you to those who have contributed $500,000 or more to The Patrick C. Walsh Prostate Cancer Research Fund.
Mr. and Mrs. Robert B. Aikens
The Ambrose Monell Foundation
Mr. and Mrs. Robert Baker Family
Mary Ann and Bill Becker
George and Mary Nell Berry
Dr. and Mrs. Peter S. Bing
Mr. Keith L. Bremer
Elva E. and William W. Carty
Jennifer A. Chalsty
John S. Chalsty
Deeks Family Foundation
R. Christian B. Evensen
Mr. Donald E. Graham
Phyllis and Brian L. Harvey
Heather C. and Patrick Henry
Charlton C. and F. Patrick Hughes
Beverly A. and Gary L. McDonald
Jean and Ian MacKechnie
Beth W. and A. Ross Myers
Nancy and Jim O’Neal
Jack W. Shay and Thomas C. Quirt
The Frank E. Rath Spang & Company
Mr. and Mrs. Paul W. Sandman
The Peter Jay Sharp Foundation
Irene and Bernard L. Schwartz
Virginia and Warren Schwerin
Donald and Susan Sturm
Carolyn and Bill Stutt
Mr. and Mrs. Charles B. Thornton, Jr.
Luciana and Joe Vittoria
For additional news and updates from the Brady Institute, please follow us on our web site at urology.jhu.edu or any of our social media sites: Facebook: Brady Urology; Twitter: @brady_urology; bradyurology.blogspot.com
From left – Beyhan Trock, Alan Partin, and Bruce Trock