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The State of The Fight

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State of the Fight: Prostate Cancer 2012

by Dr. Samuel Denmeade

State of the Fight: Prostate Cancer 2012
Samuel R. Denmeade, MD, is a Professor of Oncology at the Johns Hopkins University School of Medicine and a member of the Chemical Therapeutics Program within the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

The main goal of my research is to cure prostate cancer – a disease with which about 1 in 6 men will be diagnosed over their lifetimes. To make that goal a reality, my lab research is focused on the development of new therapies that selectively kill prostate cancer cells without harming the patient. Prostate cancer is unique among most solid malignancies in that it often grows slowly. This allows me time to develop strong relationships with my patients while managing their cancer more like a chronic disease through the administration of sequential therapies – some of which emerge over the course of their disease and can produce significant improvement in survival.

Damon Harris, a former lead singer of The Temptations, is one patient who has benefitted from this slow growth kinetic and treatment paradigm. He is a wonderful man for whom I took over as treating physician in 2009 when his former treating physician, Dr. William Nelson, was named Director of the Sidney Kimmel Comprehensive Cancer Center. Mr. Harris was diagnosed in 1998 at the age of 48 with prostate cancer based on an initial PSA level of 478 ng/mL. His cancer was thought to be that awful word that no doctor ever wants to utter: incurable.

The PSA test measures the blood level of Prostate Specific Antigen, a protein that is produced by the prostate gland. The higher a man’s PSA level, the more likely it is that he has prostate cancer. However, there are additional reasons for having an elevated PSA level, and some men who have prostate cancer do not have elevated PSA. There is no specific normal or abnormal level of PSA in the blood. In the past, most doctors considered PSA levels of 4.0 ng/mL and lower as normal. Information courtesy of the National Cancer Institute

Due to his cancer’s advanced nature, Mr. Harris did not receive any surgical or radiation treatment to his prostate, but instead underwent hormonal therapy with a dramatic and promising response. Over time though, his cancer manifested with widespread metastases in the bone. He received radiation treatment followed by chemotherapy, during which time his condition stabilized and his pain levels improved. Subsequently he participated in a clinical trial of a new drug called ipilimumab, which caused his cancer’s progression to slow.

About a year ago, I started Mr. Harris on a new drug, abiraterone acetate (Zytiga), which had just been approved as a hormone therapy for prostate cancer. His pain improved considerably, his PSA blood level decreased and his disease progression stabilized. Recently he has begun to show signs of progression once again, and is about to start MDV3100 (Xtandia) another new hormonal agent that was recently approved for prostate cancer. The great news is that Mr. Harris has resumed doing what he loves to do, performing as a singer and songwriter and even returning to the studio to release a new single.

Yet disparity is an issue for the prostate cancer research community. The hope is that future treatments can be more tailored to patients with specific genetic changes within a given tumor type. However, this research requires a broad representation of patient samples. In prostate cancer much of the information we have comes from white males. There is a great need for study of other ethnic groups, in particular African-American men, who have the highest rate of prostate cancer in the world and are nearly twice as likely to die from the disease that kills 28,000 men in the United States every year.

We have many new therapies in the pipeline for prostate cancer to help patients like Mr. Harris. For example, we need to continue to probe the role of androgen signaling in prostate cancer and look at new ways to attack the cancer based on its reliance on the function of the androgen receptor axis. We need to focus more research on rational combinational therapy. All advanced cancers that we can cure are cured by combination therapy. Thus, strategies that combine chemotherapeutic, immunologic, radiation and hormonal therapies are likely to have the best chance of success.

Patients suffering from cancer do not have the luxury of time to wait. Our focus should be on doing everything we can to speed up the pace of discovery. On an individual basis this means encouraging our lawmakers to support research funding and donating to philanthropic organizations like Stand Up To Cancer that support cancer research. New discoveries also require access and participation on the part of patients from all ethnic groups in clinical trials. Funds from the government and organizations like Stand Up To Cancer allow cancer scientists to explore new ideas and challenge existing paradigms.

We must remember that our greatest successes in medicine and public health have come in the area of prevention. It is much better to prevent childhood diseases like polio and measles through vaccination than to treat affected individuals. We currently spend a disproportionately low amount of money on cancer prevention research. Almost no pharmaceutical companies are interested in this area, due to the cost and time required to do proper studies. As a society, we need to increase investment in prevention research and, perhaps, find ways to induce more biotech and pharmaceutical companies to develop prevention programs. We must strengthen efforts to fight obesity and continue to support smoking cessation programs. We must also continue to develop better screening methodologies to identify high-risk patients based on their genetic background.

There is great reason to be optimistic about the future for patients diagnosed with prostate cancer. Currently, depending on the stage at diagnosis, 70-85% percent of men can be cured – a number that should continue to grow. Unfortunately, we still have no cure for those with disease that has metastasized outside of the prostate gland. However, our knowledge of the biological principles underlying the development and progression of cancer has grown dramatically. Every year we see new treatments that are not just being tested for prostate cancer but are receiving FDA approval based on their ability to improve survival. It’s up to all of us to ensure this lifesaving research continues.

Dr. Samuel Denmeade is a Professor of Oncology at the Johns Hopkins University School of Medicine and a member of the Chemical Therapeutics Program within the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, holding degrees from Columbia University, the Columbia University College of Physicians and Surgeons, and Johns Hopkins.

Dr. Denmeade has been the recipient of research awards from the NIH, the Department of Defense, the Prostate Cancer Foundation, the Susan Komen Breast Cancer Research Foundation, the One-in-Six Foundation and the Flight Attendants Medical Research Institute (FAMRI). He has served as the Chief Scientific Officer for Protox Therapeutics, Inc., a Vancouver based company developing PSA-activated therapies developed in Dr. Denmeade’s laboratory for the treatment of prostate cancer and benign prostatic hyperplasia. He also is the founder and serves as Chief Medical Advisor for GenSpera, Inc., a US biotechnology company that is developing protease activated prodrugs developed in Dr. Denmeade’s laboratory


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