“With this marker, I think we might have a breakthrough,” Dr. Rob Strongin, Professor of Organic Chemistry at Portland State University, said in a voice both measured and optimistic.
Dr. Strongin was referring to lysophosphatidic acid (LPA), a bioactive phospholipid that can cause cell proliferation, an ability that led researchers and physicians to implicate LPA in pathologies such as ovarian cancer and heart disease. As a biomarker, however, LPA is not without its share of controversy. LPA is notoriously difficult to work with and analyze. Opportunities for human error or contamination abound, and because LPA is nearly identical in structure to phosphatidic acid (PA), LPA can be directly generated from PA while, for example, a blood or plasma sample is waiting to be tested. Furthermore, the current method for measuring LPA is a slow, expensive, cumbersome, and unreliable process involving mass spectrometry.
Dr. Strongin believes he and his team in the Strongin Group have found a way to put the controversy over LPA to rest while helping scientists and medical doctors determine if LPA can be used to detect ovarian cancer in its early stages.
With a grant from the National Institutes of Health (NIH), and in association with researchers at Brown University’s Alpert Medical School Women & Infants Hospital, Dr. Strongin along with Strongin Group team members Dr. Martha Sibrian-Vazquez, Dr. Jorge Escobedo, and graduate students Jialu Wang, Shelly Chu, and Lei Wang have developed a novel method for isolating LPA in blood or plasma samples, after which a technique called high-performance liquid chromatography (HPLC) and a simple spectrometer found in any chemistry lab can be used to quantify levels of LPA. The innovative method of measuring LPA developed by Dr. Strongin and his team is clean, simple, and can be standardized. With such a tool, researchers studying LPA could eliminate occurrences of false positives in their research and pursue studies to determine if LPA is indeed a good biomarker for early stage ovarian cancer detection.
“Using our methods,” Dr. Strongin said, “we can bypass other tests and run hundreds of samples a day without specialized equipment.”
Running tests on blood samples is exactly what Dr. Strongin and his team have done. The samples are now in the hands of Dr. Richard Moore, an expert in obstetrics and gynecology, who, with the resources of the Women and Infants Hospital in Rhode Island, is reviewing the team’s results.
“It would be wonderful if this method helped us determine if LPA was a good indicator for early stage ovarian cancer,” Dr. Strongin said. “There are thousands of people dying every year from this disease, and the thing is, it’s curable. There’s a high rate of recovery if physicians detect the cancer in stage one. If they can find it, they can take action.”
If they can find it…
Ovarian cancer has been called a silent killer. Silent, because this cancer is all too frequently diagnosed in late stages, after the cancer has metastasized and chances of recovery have dropped into single digits. The lack of early detection—only one if five cases are found at stage one or two—can be attributed, in part, to how common and unassuming early symptoms are: fatigue, irritation of the digestive track, bloating, and pain in the abdomen, pelvis, back, or legs—all symptoms that occur in any number of conditions. If LPA proves to be an indicator of early stage ovarian cancer it will help save the lives of thousands of women every year and allow thousands more to avert the need to pursue aggressive treatment options such as chemotherapy, radiation therapy, or immunotherapy.
“The aim of our work,” said Dr. Jorge Escobedo, a colleague and longtime collaborator of Dr. Strongin’s, “is to help doctors prevent the cancer from spreading instead of going after the cancer in later stages with harsh treatments.”
When asked about potential applications this new method for detecting LPA might lead to, Dr. Strongin responded: “We hope that leads to a routine point-of-care diagnostic test, something a general practitioner could use in the office and not have to send off to a lab for analysis.” While working on a method for isolating and measuring LPA, Strongin Group team members were also developing organic dyes that exhibit a color or fluorescence change when they come into contact with specific biomaterials, in this case LPA. In the hands of a medical diagnostics company these two innovations could be combined to produce a simple, easily-stored ovarian cancer test that could save lives around the world.
“We are very excited about this work,” said Joe Janda, Director of Innovation & Intellectual Property (IIP) at PSU. “These are extremely important technologies to pursue. The impacts on lives and health could be enormous, and we very much look forward to helping these innovations move out of the University and into the public sphere where they can be used to the greatest effect.”
“We decided to take on a really big problem,” Dr. Strongin said. “We took classic organic chemistry and put it to work to save peoples’ lives. And though there’s no certainty LPA will turn out to be a good biomarker for early stage ovarian cancer, we know it’s involved in cardiovascular disease, so we can still develop an assay that will be of use. But we think there’s a high probability LPA will be a good indicator of early stage ovarian cancer.”
The late detection of ovarian cancer is an ongoing public health crisis. The National Cancer Institute estimates 22,280 new cases will be reported in the United States in 2012; the Institute expects 15,000 women will die of the disease. If Dr. Strongin is right, and LPA proves to be a breakthrough biomarker for the early detection of ovarian cancer, the technology he and his team have developed will have a profound impact. When detected at an early stage, 94 percent of patients live longer than five years after diagnosis. A point-of-care test like the one Dr. Strongin envisions could lead to a dramatic decrease in the number of people who die from ovarian cancer every year. That is why Dr. Strongin and the Strongin Group represent some of the best of what Portland State University innovators have to offer.
Authored by Shaun McGillis
Posted December 18, 2012