Inaugural SBP Insights speaker series highlights prostate cancer
AuthorHelen Hwang
Date
March 20, 2018
In the first SBP Insights speaker series, the Institute hosted a doctor, scientist and patient to take a 360-degree look at prostate cancer. Prostate cancer impacts one in nine men, according to the Prostate Cancer Foundation, but the panel experts said the statistic rises dramatically as men get older.
Nick Cosford, PhD, deputy director of SBP’s NCI-designated Cancer Center, discussed how his research is leading to pioneering treatments for advanced prostate cancer by harnessing autophagy (“self-eating” in Greek), a normal physiological process in the body that deals with the destruction of cells.
First diagnosed with prostate cancer more than 20 years ago, SBP Board Chairman Hank Nordhoff shared stories of his own personal experience and how far treatment has progressed since then.
Christopher Kane, MD, senior deputy director of Moores Cancer Center and professor and chair of urology at UC San Diego, gave a clinical perspective on prostate cancer diagnosis and treatment. He shared how if examined closely, nearly half of all 70-year-old men will have low-volume, low-grade prostate cancer. His advice about age and surgical treatments: “You should only have surgery if you can still bring your dad to see me.”
Brad Wills, FOX5 morning weather anchor, moderated the event with great charisma and humor, helping the audience deal with a serious subject in a light-hearted way.
Nearly 90 people from the community attended the unique panel presentation and Q&A, during which audience members had the opportunity to ask the experts about the latest breakthroughs in finding a cure for prostate cancer.
Join us for a unique, 360-degree look at Alzheimer’s disease. The next SBP Insights speaker event takes place on June 5, featuring a panel presentation with leading experts followed by a Q&A. Dr. Jerold Chun, senior vice president of neuroscience drug discovery, Dr. Michael Lobatz, medical director of the Rehabilitation Center at Scripps Memorial Hospital Encinitas, and Serena Reid, a caregiver for an Alzheimer’s disease patient. Kristen Cusato, associate director of the Alzheimer’s Association, will be moderating.
Institute News
Beating prostate cancer
Authorjmoore
Date
November 7, 2016
About one in seven men will be diagnosed with prostate cancer during his lifetime. Though it has one of the highest survival rates of any type of cancer—95% make it through the first ten years—diagnosis and treatment could still be improved. Since November is Prostate Cancer Awareness Month, we’re highlighting the work our scientists are doing to address key challenges and unresolved questions in prostate cancer.
Early, accurate detection—The current method of screening for prostate cancer is a blood test for prostate specific antigen, or PSA, which detects cancer early, but isn’t very specific—only one in four men with high PSA levels actually has cancer. In general, high levels of PSA mean the next step is a biopsy. A more specific test would avoid unnecessary biopsies, which are invasive and stressful for patients.
Ranjan Perera, PhD, associate professor in the Integrative Metabolism Program, is looking for biomarkers that would enable just such a test. His lab is making progress—they identified five long noncoding RNAs (RNAs that, instead of carrying genetic information to be translated, regulate the translation of other RNAs) found at higher-than-normal levels in the urine of prostate cancer patients. An RNA-based test is on the market, but could be improved—measuring multiple markers would be more sensitive and specific.
Better therapies—For advanced cases, current treatments are either insufficient or overly toxic. Prostate cancer is usually first treated with drugs that block the actions of androgens, the hormones that drive its growth. If the tumor recurs later, as happens for cancers that are already at a late stage before treatment, it forms from cells that are resistant to those drugs. Then, the only option is chemotherapy or radiation.
Towards therapies that cause less collateral damage, Nicholas Cosford, PhD, associate director of Translational Research in the NCI-designated Cancer Center, is designing new drugs against targets found to be important in prostate cancer. These drugs are intended to block two strategies by which cancer cells survive—avoiding cell death, and generating extra energy by recycling the cell’s own parts.
Understanding why obesity correlates with aggressiveness—Obese men are no more likely than others to get prostate cancer, but if they do, it’s more likely to become advanced quickly. To figure out why this happens, Jorge Moscat, PhD, director, and Maria Diaz-Meco, PhD, professor in the Cancer Metabolism and Signaling Networks Program, are looking at how fat adjacent to the prostate interacts with tumor cells. A detailed picture of how fat cells and tumor cells interact could reveal new ways to treat prostate cancer in overweight men.
Institute News
New molecular markers for prostate cancer identified
Authorsgammon
Date
October 9, 2014
A team of scientists led by Sanford-Burnham’s Ranjan J. Perera, PhD, has identified a set of RNA molecules that are detectable in tissue samples and urine of prostate cancer patients, but not in normal healthy individuals. The study sets the stage for the development of more-sensitive and specific non-invasive tests for prostate cancer than those currently available, which could result in fewer unnecessary prostate biopsies with less treatment-related morbidity, according to a new study in The Journal of Molecular Diagnostics.
According to the American Cancer Society, prostate cancer is the second most common type of cancer in American men (behind skin cancer), and the second-leading cause of cancer death in men (after lung cancer). In 2014, more than 230,000 new cases of prostate cancer will be diagnosed. One in seven American men will get prostate cancer during his lifetime, and one in 36 will die from it. Since most men with prostate cancer have indolent (non-aggressive) disease for which conservative therapy or surveillance would be appropriate treatment, the clinical challenge is not only how to identify those with prostate cancer, but also how to distinguish those who would benefit from surgical or other aggressive treatment from those who would not.
Today, prostate cancer is primarily detected and monitored by testing for high concentrations of prostate-specific antigen (PSA) in blood samples. High PSA levels are often followed by a biopsy to confirm the presence of cancer, and whether it’s slow growing or aggressive. “While elevated PSA can be an alert to a lethal cancer, it can also detect less aggressive cancers that may never do any harm,” said Vipul Patel, MD, medical director of the Global Robotics Institute at Florida Hospital in Orlando, and co-author of the study. “Moreover, only 25 percent of men with raised PSA levels that have a biopsy actually have prostate cancer. Prostate cancer needs to be screened for; we just need to find a better marker.”
The researchers believe that they have identified a group of RNA molecules – known as long noncoding RNAs (lncRNAs) – that hold the potential for serving as better prognostic markers for prostate cancer. lncRNAs are noncoding RNA molecules that until recently were dismissed by scientists as non-functional noise in the genome. Now, lncRNAs are thought to regulate normal cellular development and are increasingly reported as contributing to a range of diseases, including cancer.
Detection of lncRNAs in urine
“We have identified a set of lncRNAs that appear to have an important role in prostate cancer diagnostics,” said Perera, associate professor and scientific director of Analytical Genomics and Bioinformatics at our Lake Nona campus. “The findings advance our understanding of the role of lncRNAs in cancer biology and, importantly, broaden the opportunity to use lncRNAs as biomarkers to detect prostate cancer.”
The study profiled the lncRNAs in three distinct groups: (1) human prostate cancer cell lines and normal prostate epithelial cells, (2) prostate adenocarcinoma tissue samples and matched normal tissue samples, (3) urine samples from patients with prostate cancer or benign prostate hypoplasia, and normal healthy individuals. In each case, the lncRNAs were elevated in prostate cancer patient samples, but not in patients with benign prostate hypoplasia or normal healthy individuals.
One advantage of lncRNAs is that the molecules can be detected in urine samples, which are more easily available than blood tests. One lncRNA, PCA3, was recently commercialized as a urine test to identify which men suspected of having prostate cancer should undergo repeat prostate biopsy. However, discrepancies have been found to exist between PCA3 levels and clinicopathologic features, said Perera. In the current study, PCA3 was detected in some, but not all of the study samples, suggesting that reliance on a single biomarker may be insufficient for prostate cancer detection, while combining additional markers may increase the specificity and sensitivity of the test.
“There is a tremendous unmet clinical need for better non-invasive screening tools for early detection of prostate cancer to reduce the overtreatment and morbidity of this disease,” added Patel. “Our findings represent a promising approach to meet this demand.”
Technical details of the study
The goal of the first experiment was to see whether lncRNAs are differentially expressed in prostate cancer by measuring total RNA from prostate cancer cell lines and normal epithelial prostatic cells using NCode human ncRNA array and SurePrint G3 human lncRNA microarrays. Hierarchical clustering revealed distinguishable lncRNA expression profiles. Thirty lncRNAs were up-regulated and the expression levels of three top-ranking candidates [XLOC_007697, LOC100287482, and AK024556 (also known as SPRY4-IT1)] were confirmed in prostate cancer cell lines by quantitative real-time polymerase chain reaction (qPCR) analysis. The SPRY4-IT1 was found to be up-regulated more than 100-fold in PC3 cells compared with prostatic epithelial cells.
In a second experiment, lncRNA expression was compared in pooled prostate cancer tissue samples and matched normal tissues from 10 frozen biopsy specimens. Hierarchical clustering of the differentially expressed lncRNAs was observed and 10 up-regulated lncRNAs were detected using microarrays. An additional set of 18 prostate cancer tissue samples was analyzed by qPCR and five lncRNAs were found to be significantly higher in prostate tumor tissues compared with matched normal tissues.
Researchers used qPCR to analyze total RNA isolated from urine in another experiment. Urine was collected from 13 prostate cancer patients and 14 healthy controls. All six lncRNAs were found to be significantly up-regulated in the urine samples from the prostate cancer patients compared with normal patient controls, while there were no differences between normal and benign prostatic hyperplasia patient samples.
In other studies focused particularly on SPRY4-IT1. Using both qPCR and highly sensitive droplet digital PCR, expression of SPRY-IT1 was found to be increased in 16 of 18 (89 percent) tissue samples from patients with prostatic adenocarcinoma, compared to normal tissue samples. The researchers developed chromogenic in situ hybridization (CISH) techniques to visualize SPRY4-IT1 expression in cancerous and matched normal tissue. Intense staining was seen in all adenocarcinoma samples, but not in normal prostatic tissue. Finally, the investigators showed that reduction of SPRY4-IT1 in prostate cancer cells through the use of small interfering RNA (siRNA) leads to decreased cell viability and cellular invasion as well as increased apoptosis, similar to what is seen in melanoma cells.
About the paper
“Long Noncoding RNAs as Putative Biomarkers for Prostate Cancer Detection,” by Bongyong Lee, Joseph Mazar, Muhammed Nauman Aftab, Feng Qi, John Shelley, Jian-Liang Li, Subramaniam Govindarajan, Felipe Valerio, Inoel Rivera, Tadzia Thurn, Tien Anh Tran, Darian Kameh, Vipul Patel, and Ranjan J. Perera, DOI: http://dx.doi.org/10.1016/j.jmoldx.2014.06.009. Published online ahead of The Journal of Molecular Diagnostics, Volume 16, Issue 6 (November 2014) published by Elsevier.
