Research in the News
Jack Andraka: A promising teen scientist is raising national awareness and bringing the topic of pancreatic cancer into living rooms around the world
Maryland teenager Jack Andraka won some exciting awards last year, including first prize at the Intel International Science and Engineering Fair, for his work in exploring diagnostic tools for early detection of pancreatic cancer. On Sunday, October 13, 2013 Jack was profiled in a segment on CBS’ 60 Minutes. We are thrilled that Jack is so enthusiastic and passionate about making progress in pancreatic cancer and we are grateful that he is spurring a national conversation about the need for an early detection test for one of the deadliest cancers.
Jack’s original project involved a dipstick technology, whereby a small piece of paper is coated with antibodies that are designed to specifically recognize particular proteins that circulate in the blood or urine of patients with pancreatic cancer, but not individuals without the disease. As indicated on 60 Minutes, his work is still in the early stages and will require many more years of research, but we look forward to one day in the future when an idea like Jack’s leads to an early detection test that is available to the public.
Just as Jack has done, let’s continue to make pancreatic cancer part of the national discussion. Detailed information about the state of scientific research for early detection of pancreatic cancer can be found below.
What do we know about the ability of Jack’s test to detect pancreatic cancer?
The dipstick technology that Jack utilized for his project involved a small piece of paper coated with antibodies that are connected to a device called a nanotube. The antibodies recognize proteins that circulate in the blood or urine of patients with pancreatic and some other forms of cancer, but not individuals without the disease. Like a home pregnancy or diabetes test, this technology is much quicker and less expensive than standard laboratory tests. The studies Jack performed show that the test he developed for the protein he is interested in, called mesothelin, is a good, reliable method to detect very low levels of the protein in the bloodstream of both mice and people.
Jack performed his experiments in the laboratory of Anirban Maitra, MBBS, then at Johns Hopkins University (Dr. Maitra has relocated to MD Anderson Cancer Center). Dr. Maitra is a leader in the pancreatic cancer field, recipient of a 2004 Pancreatic Cancer Action Network Career Development Award, and Chair of the Pancreatic Cancer Action Network Scientific Advisory Board. Jack showed in mouse studies that the levels of mesothelin are higher in the bloodstream of mice with pancreatic cancer compared to healthy mice. He also tested some samples from patients with and without advanced pancreatic cancer, and again found that mesothelin levels are higher in the individuals who have been previously diagnosed with the disease. These preliminary results are encouraging, although it will be necessary to test more samples and perform more experiments before knowing whether Jack’s test can accurately detect pancreatic cancer at its early stages.
The best opportunity for a positive outcome is when pancreatic cancer is diagnosed early, when the patient might be eligible for surgery. However, we do not yet know how much mesothelin is circulating in the bloodstream of patients with either early stage pancreatic cancer or those with pre-cancer.
How is pancreatic cancer currently diagnosed?
There is no standard diagnostic test for pancreatic cancer; however, there are multiple imaging techniques that are used to detect the disease, including specialized types of ultrasound, CT scan, and MRI. In a process called a biopsy, a small piece of tumor tissue is removed and examined under a microscope to definitively diagnose pancreatic cancer.
Scientists are working to develop a simple blood or urine test that could be used to screen many people and identify those who should be further examined by these imaging techniques because they may have very early stages of pancreatic cancer. In order to achieve this, many studies are devoted to identifying compounds in the blood or urine, called biomarkers, that could be useful in the diagnosis of pancreatic cancer. One of the biggest challenges facing these scientists is to find people who have very early-stage pancreatic cancer to test if the biomarker works. Several groups of scientists are examining individuals who are at high risk for developing the disease, including those with a strong family history of pancreatic cancer, as a way of testing whether any of these biomarkers are useful for detecting pancreatic cancer at early stages.
What is a biomarker?
A biomarker is a substance found in the body that can be measured. The amount of a biomarker may vary between a healthy individual and someone with a disease, therefore potentially aiding in diagnosis of that disease. In addition, biomarkers can sometimes be used to predict a patient’s response to a specific treatment, or to monitor whether a treatment is effective in a particular patient.
A recent review article in a biomedical journal found that more than 2,000 studies have been published evaluating more than 2,000 genes as potential biomarkers for pancreatic cancer. However, the only biomarker currently approved by the Food and Drug Administration (FDA) for use in pancreatic cancer is called CA19-9 (serum carbohydrate antigen 19-9). But, large-scale studies have shown that measuring CA19-9 levels is not useful for screening high-risk individuals or diagnosing pancreatic cancer. Instead, in patients whose tumors express the CA19-9 biomarker, levels can be monitored and may indicate whether a patient is responding to a treatment and whether the disease has recurred.
How do you determine whether a biomarker will work?
In order to become an FDA-approved pancreatic cancer biomarker that can aid in the diagnosis of the disease, rigorous experimentation is necessary. First, scientists in a laboratory analyze samples (can be blood, tissue, urine, pancreatic juice, or others) from pancreatic cancer patients to determine if there are genes, proteins, or other markers that are expressed in these patients, but not healthy individuals. A candidate biomarker has to be consistently and accurately measurable and there has to be a statistically significant difference in expression levels between specimens from pancreatic cancer patients and healthy individuals. One gene or protein is not usually enough to be sufficiently accurate – some tests now involve using several biomarkers to reduce the chance of getting false negative or false positive results and improve the value of the test.
Next, it is necessary to validate the potential biomarker in a larger number of samples in a retrospective manner. Retrospective means that the researchers are looking at samples from people who have already been diagnosed with pancreatic cancer. Again, it’s important that the biomarker can be consistently measured and always shows a significant distinction between pancreatic cancer cases and healthy individuals.
Once the biomarker (or panel of several biomarkers) has shown success in retrospective analyses, it’s necessary to undergo prospective, or forward-looking, studies. In order to be considered a viable diagnostic biomarker, it would have to accurately identify disease at early or precancerous stages. This type of study would take place as a formal clinical trial. People eligible for the trial would be those considered at high risk for developing pancreatic cancer. These people would be monitored to see if they develop the disease. It would take a large number of participants to allow for a significant enough subset of people to go on to develop the disease. Therefore, people would have to be watched and monitored over the course of many years.
These types of studies are expensive and time-consuming. While other biomarkers have been validated for use in the diagnosis of other cancer types, the pancreatic cancer field is still searching for a biomarker (or biomarkers) that could identify people with early stages of the disease. There are studies underway at various steps in the process of validating biomarkers. One of the furthest along is the CAPS (cancer of the pancreas screening study) taking place primarily at Johns Hopkins University, that is partially funded by the Pancreatic Cancer Action Network Inaugural Research Acceleration Network (RAN) Grant in memory of Skip Viragh. Although progress has been made, it will still be several years before the biomarkers being evaluated in the CAPS study could be considered validated for pancreatic cancer, and eligible for FDA approval. Other biomarker studies are also progressing nicely towards becoming novel early detection methods for pancreatic cancer.
We look forward to the day when an idea like Jack’s leads to an early detection test that is available to the public. Before we can know whether Jack’s idea could be useful as a diagnostic tool for pancreatic cancer, further testing of a larger sampling of retrospective samples will be necessary, followed by the extensive prospective trial outlined above. Overall, it is a complex process to discover biomarkers that can aid in the diagnosis of pancreatic cancer. After identifying candidate biomarker or biomarkers, researchers must make sure that they are consistently measurable and clearly differentiate pancreatic cancer cases from healthy individuals. Then they must test the biomarker(s)’ accuracy in a large group of people already diagnosed with pancreatic cancer, compared to healthy individuals. The final step of this process, a prospective clinical trial, is the most arduous and, unfortunately, where most candidate biomarkers do not succeed. Even the only FDA-approved biomarker for pancreatic cancer, CA19-9, has failed to be an accurate indicator of early disease. Brilliant scientists and clinicians across the US and the world are working tirelessly to identify and validate biomarkers that could aid in the earlier diagnosis of pancreatic cancer. The Pancreatic Cancer Action Network’s goal is to continue to build a critical mass of scientists focused on pancreatic cancer. We hope that other young people will take Jack’s lead and pursue an interest in science or medicine. We applaud Jack’s relentless pursuit in working hard to detect pancreatic cancer as early as possible.
For more information about diagnosing pancreatic cancer or other questions about the disease, please contact a Pancreatic Cancer Action Network Patient and Liaison Services (PALS) Associate toll-free at 877-272-6226 or email firstname.lastname@example.org. PALS Associates are available M-F 7am-5pm Pacific Time.