Cleveland Clinic researchers reveal biomarker for guiding prostate cancer treatmentOctober 12, 2017
October 12, 2017, Cleveland: Back-to-back discoveries from Cleveland Clinic demonstrate for the first time how a testosterone-related genetic abnormality can help predict individual patient responses to specific prostate cancer therapies.
The studies, published in the October 12 issue of JAMA Oncology, suggest that men who inherit this variant would benefit from a personalized treatment plan that targets specific hormonal pathways.
The research teams, led by Nima Sharifi, M.D., of the Cleveland Clinic Lerner Research Institute, studied the role of the HSD3B1(1245C) genetic variant in two different prostate cancer patient populations, following androgen deprivation therapy (ADT). ADT works by blocking prostate cancer's supply of male hormones in the testes. It is a cornerstone treatment for recurrent prostate cancer, but it often stops working, allowing cancer to progress and spread. In 2013, Dr. Sharifi discovered that prostate cancer cells with the genetic abnormality survive ADT by producing their own androgens.
In the first new study, Dr. Sharifi and colleagues from Memorial Sloan Kettering Cancer Center, Harvard/Dana-Farber Cancer Institute and University of Michigan Comprehensive Cancer Center analyzed 213 men whose prostate cancer recurred after radiation therapy and underwent ADT. They found for the first time that following radiation and ADT, prostate cancer was much more likely to spread--and spread rapidly--in men who had the HSD3B1(1245C) variant.
The second study, performed in collaboration with researchers at University of California San Francisco, examined a group of 90 men with metastatic cancer that had become resistant to ADT. These patients were subsequently treated with the drug ketoconazole, which blocks the production of androgens outside of the testes (e.g., those developed by prostate cancer cells that are evading ADT treatment).
Surprisingly, men with the genetic anomaly fared better on ketoconazole than men without the variant. This finding raises the possibility that targeting variant tumors' backup androgen supply (outside of the testes) could be a successful strategy when ADT fails.
"We hypothesized that HSD3B1(1245C) variant tumors become resistant to ADT because they have a backup supply of androgens," said Dr. Sharifi. "However, relying on these extra-gonadal androgens makes them more sensitive to ketoconazole."
These discoveries complement earlier studies and support the use of HSD3B1(1245C) as a predictive biomarker to help guide critical treatment decisions. While the outlook of patients with this gene variant is poor, these studies offer hope for a new treatment strategy for these men, and more studies are needed using next-generation androgen inhibitors, such as abiraterone and enzalutamide.
"We are hopeful that these findings will lead to more personalized and effective treatments for prostate cancer," said Dr. Sharifi. "If men carry a specific testosterone-related genetic abnormality we may be able to personalize their therapy and treat specific patients more aggressively."
Dr. Sharifi is also a member of the Glickman Urological and Kidney Institute and Taussig Cancer Institute of Cleveland Clinic. He holds the Kendrick Family Chair for Prostate Cancer Research at Cleveland Clinic and co-directs Cleveland Clinic's Center of Excellence for Prostate Cancer Research. In 2017 he received a Top Ten Clinical Research Achievement award from the Clinical Research Forum for his landmark discovery that men who carry the HSD3B1(1245C) variant are more likely to die from their disease.
About Cleveland Clinic
Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S. News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. Among Cleveland Clinic's 51,000 employees are more than 3,500 full-time salaried physicians and researchers and 14,000 nurses, representing 140 medical specialties and subspecialties. Cleveland Clinic's health system includes a 165-acre main campus near downtown Cleveland, 10 regional hospitals, more than 150 northern Ohio outpatient locations - including 18 full-service family health centers and three health and wellness centers - and locations in Weston, Fla.; Las Vegas, Nev.; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2016, there were 7.1 million outpatient visits, 161,674 hospital admissions and 207,610 surgical cases throughout Cleveland Clinic's health system. Patients came for treatment from every state and 180 countries. Visit us at clevelandclinic.org. Follow us at twitter.com/ClevelandClinic.
Editor's Note: Cleveland Clinic News Service is available to provide broadcast-quality interviews and B-roll upon request.
About the Lerner Research Institute
The Lerner Research Institute is home to Cleveland Clinic's laboratory, translational and clinical research. Its mission is to promote human health by investigating in the laboratory and the clinic the causes of disease and discovering novel approaches to prevention and treatments; to train the next generation of biomedical researchers; and to foster productive collaborations with those providing clinical care. Lerner researchers publish more than 1,500 articles in peer-reviewed biomedical journals each year. Lerner's total annual research expenditure was $260 million in 2016 (with $140 million in competitive federal funding, placing Lerner in the top five research institutes in the nation in federal grant funding). Approximately 1,500 people (including approximately 200 principal investigators, 240 research fellows, and about 150 graduate students) in 12 departments work in research programs focusing on heart and vascular, cancer, brain, eye, metabolic, musculoskeletal, inflammatory and fibrotic diseases. The Lerner has more than 700,000 square feet of lab, office and scientific core services space. Lerner faculty oversee the curriculum and teach students enrolled in the Cleveland Clinic Lerner College of Medicine (CCLCM) of Case Western Reserve University - training the next generation of physician-scientists. Institute faculty also participate in multiple doctoral programs, including the Molecular Medicine PhD Program, which integrates traditional graduate training with an emphasis on human diseases. The Lerner is a significant source of commercial property, generating 64 invention disclosures, 15 licenses, 121 patents, and one new spinoff company in 2016. Visit us at http://www.lerner.ccf.org. Follow us on Twitter at http://www.twitter.com/CCLRI.
Related Prostate Cancer Articles:
The American Society of Clinical Oncology (ASCO) and Cancer Care Ontario today issued a joint clinical practice guideline update on brachytherapy (internal radiation) for patients with prostate cancer.
For the first time, researchers have been able to grow, in a lab, both normal and primary cancerous prostate cells from a patient, and then implant a million of the cancer cells into a mouse to track how the tumor progresses.
Moffitt researchers David Basanta, Ph.D., and Conor Lynch, Ph.D., have been awarded a U01 grant to investigate prostate cancer metastasis.
For the first time ever, researchers have differentiated the risks of developing indolent or aggressive prostate cancer in men with a family history of the disease.
A newly discovered connection between two common prostate cancer treatments may soon make prostate cancer cells easier to destroy.
A study from Karolinska Institutet in Sweden shows that a new test for prostate cancer is better at detecting aggressive cancer than PSA.
Primary care providers are put in a difficult position when screening their male patients for prostate cancer -- some guidelines suggest that testing the general population lacks evidence whereas others state that it is appropriate in certain patients.
New research suggests that age, race and family history are the biggest risk factors for a man to develop prostate cancer, although high blood pressure, high cholesterol, vitamin D deficiency, inflammation of prostate, and vasectomy also add to the risk.
Cancer Research UK scientists have for the first time identified that there are five distinct types of prostate cancer and found a way to distinguish between them, according to a landmark study published today in EBioMedicine.
The radiation oncology team at UH Seidman Cancer Center in Cleveland performed the first-ever prostate cancer treatment April 3 using a newly-approved device -- SpaceOAR which enhances the efficacy of radiation treatment by protecting organs surrounding the prostate.
Related Prostate Cancer Reading:
Dr. Patrick Walsh's Guide to Surviving Prostate Cancer
by Patrick C. Walsh (Author), Janet Farrar Worthington (Author)
Each year, more than 230,000 men are diagnosed with prostate cancer, and 30 to 40 percent of patients who are diagnosed will eventually relapse. But the good news is that more men are being cured of this disease than ever before. Now in a revised third edition, this lifesaving guide by Dr. Patrick Walsh and award-winning 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. Readers will discover their risk factors, simple changes that can... View Details
Prostate Cancer: A New Approach to Treatment and Healing
by Dr. Emilia A. Ripoll (Author), Mark B. Saunders (Author)
Prostate Cancer: A New Approach to Treatment and Healing gives readers new access to leading-edge medical information about prostate cancer, by making it simple and easy-to-understand. Essentially, this is a picture book for adults, written in everyday English, with lots of state-of-the-art information to support all the images, flow charts, tables, and diagrams. Each chapter has a patient story, doctor story, and interactive Toolbox section. The book also contains a Spouses Section (because no one goes through a prostate cancer diagnosis alone) and a Digging Deeper section for readers... View Details
You Can Beat Prostate Cancer: And You Don't Need Surgery to Do It
by Robert J. Marckini (Author)
The task of choosing the right prostate cancer treatment is daunting. It is further complicated by conflicting information the patient receives from physicians and the Internet. This book is written by a prostate cancer survivor who now runs an international prostate cancer support group. It's about his journey and the important things he learned along the way. It is the book the author wishes had been available when he was diagnosed 6 years ago. It is intended to provide specific information for men who are at risk or have been recently diagnosed with prostate cancer. All major treatment... View Details
Prostate and Cancer: A Family Guide to Diagnosis, Treatment, and Survival
by Sheldon Marks (Author)
Prostate cancer is one of the most common cancers affecting American men, with over 186,000 new cases diagnosed in the United States annually; 1 in 6 men will be diagnosed with prostate cancer during his lifetime. Renowned prostate cancer specialist Sheldon Marks offers the definitive guide for men concerned about or diagnosed with prostate cancer, and for their families.
Since the third edition (2003), there have been significant changes in treatment and resources. Working with Dr. Judd Moul, the Chairman of Urology at Duke and one of the world's top experts on prostate cancer, Marks... View Details
100 Questions & Answers About Prostate Cancer
by Pamela Ellsworth (Author)
100 Questions & Answers About Prostate Cancer provides authoritative and practical answers to the most common questions asked by patients and their loved ones. Providing both doctor and patient perspectives, this easy-to-read book is a comprehensive guide to the basics of prostate cancer, risk factors and prevention, diagnosis, treatment, survivorship, and life after diagnosis. Written by Dr. Pamela Ellsworth, a prominent urologist and best-selling author, Questions & Answers About Prostate Cancer is an invaluable resource for anyone interested in learning what to expect after being diagnosed... View Details
Thrive Don't Only Survive: Dr.Geo's Guide to Living Your Best Life Before & After Prostate Cancer
by Dr. Geo Espinosa (Author)
Prostate cancer is not the end—it’s the beginning. It’s the point where you start taking control.
Information on what to do isn't hard to find. There are dozens of books on prostate cancer, as well as a massive amount of online resources. What's lacking, however, is a trusted, reliable source on implementing the abundance of scientific evidence in a way that’s realistic and sustainable.
Based on his extensive research and clinical experience on natural medicine for prostate problems, Dr. Geo has created a lifestyle blueprint that men can apply immediately to thrive before or... View Details
"Prostate Cancer Breakthroughs 2014: New Tests, New Treatments, Better Options: A Step-by-Step Guide to Cutting-Edge Diagnostic Tests and 12 Medically-Proven Treatments
by Jay S. Cohen (Author)
"Vital new information for men diagnosed with prostate cancer!" --George Johnson, Director of the Informed Prostate Cancer Support Group in San Diego, the largest independent group in California
"I have had treatment for prostate cancer and have been thru the mill. If I were going to go through the process again, I would start with Dr Cohen's book." --P.C., independent review at Amazon.com
Updated for 2014, Prostate Cancer Breakthroughs 2014 offers 55 additional pages from the original top-selling book. Also, new information on PSA testing, how to obtain a new targeted biopsy,... View Details
The Definitive Guide to Prostate Cancer: Everything You Need to Know about Conventional and Integrative Therapies
by Aaron Katz (Author)
The complete guide to coping with prostate cancer, with expert health advice for every man
This comprehensive handbook gives men the vital information they need to effectively navigate every
step of dealing with prostate cancer. A newly diagnosed cancer patient faces a mind-numbing array of treatment options, including medical therapies that carry serious side effects―and determining the right course of action is an overwhelming task. In simple yet scientific terms, this book empowers readers with the tools they need to proactively fight cancer by making the most informed treatment... View Details
The Prostate Health Diet: What to Eat to Prevent and Heal Prostate Problems Including Prostate Cancer, BPH Enlarged Prostate and Prostatitis
by Ronald M Bazar (Author), Coreen Boucher (Editor)
Do you know the best diet for your prostate gland?
Do you know the best diet for preventing or curing prostate cancer?
Do you know the best diet for your prostate health and to prevent prostate disease?
Most men don’t.
The Prostate Health Diet shows you how to find the best diet for you and how to customize your diet for optimum health and your uniqueness.
The Prostate Health Diet is not a fad diet. It will guide you to find what will work for you with practical insights into the often conflicting views of what you... View Details
Prostate Cancer For Dummies
by Paul H. Lange (Author), Christine Adamec (Author)
Hearing that you have prostate cancer, or even that you may have it, is very scary. But this disease, in many cases, is curable. Even if you have advanced cancer that's spread beyond the prostate, many treatments help extend your life for years. You need good information to help you with the decisions that lie ahead, and this book provides you with this information.
Prostate Cancer For Dummies can help you ifYou have prostate cancer (or you think that you have it), or someone close to you has it. You want information on treatments for prostate cancer as you form a treatment... View Details