Biomarkers are biological substances that can be measured to indicate some state of disease. They can be used to detect a disease early, diagnose a disease, track the progression of the disease, predict how quickly a disease will progress, determine what the best treatment is for the disease, or monitor whether or not a treatment is working. Biomarkers have the potential to do so much, and identifying biomarkers for different steps in the health/disease continuum would help doctors to provide each individual with targeted, precision healthcare. Biomarkers have the potential to save billions of healthcare dollars by helping prevent disease, by treating disease early (when it's usually less expensive to treat), or by targeting treatments and avoid giving a treatment that won't be effective.
With all this potential, you would expect doctors to be using data from biomarkers to guide every single healthcare decision - but this isn't the case quite yet. First scientists have to find these biomarkers - a process often referred to as biomarker discovery. I like to compare finding a biomaker to those "spot the differences" games where you have to look at two images and circle what is different in one picture compared to the other. This is exactly what scientists do when finding a biomarker, except instead of comparing pictures, they are comparing patients. And it's not an easy game of "spot the differences" it's complicated: the pictures are small and there are tons of details.
Let's imagine a scenario that a scientist might face when wanting to find a biomarker for the early detection of pancreatic cancer. Cancer is caused by mutations in the DNA, so you decide to look for DNA mutations as your biomarker for pancreatic cancer. So how do you "spot the differences" to find DNA biomarkers for pancreatic cancer? First, you will need patient samples - maybe tissue or blood samples from a biobank that already has samples from patients with pancreatic cancer. If samples aren't already available, you will have to initiate a study partnering with doctors to collect samples from pancreatic cancer patients for you. You will also need the second "picture" to compare the pancreatic cancer "picture" to. This second picture will be samples from people who don't have pancreatic cancer (scientists usually call this group the "control" group). Then you have to "look" at the two groups' DNA so you can find those differences. This "looking" is often done by some genomics method like sequencing the DNA. This is where a lot of the complication comes in because if you look at all of the DNA, you will be comparing 3 billion individual nucleotides (the A, T, G, and Cs we've discussed in earlier posts) from each patient to each of the controls. Even if you just look at the DNA that makes proteins, you're still comparing 30 million nucleotides per patient. And you can't just compare one patient to one control! Each of us is genetically different by ~1%, so you need to compare many patients to many controls to make sure that you find DNA that is involved in the disease and not just the ~1% that is already different between individuals. But wait, we're not done yet! The biomarkers that you identify have to be validated - or double checked - to make sure that these differences just weren't found by mistake. And before biomarkers can be used in the clinic, they need to be approved by the Food and Drug Administration (FDA).
Whew... that was a lot of work! And so many people were involved: lead scientists who directed the project and got the money to fund it, researchers who do most of the work, computer people who are experts at crunching all of the data, and maybe even engineers to help run the equipment. Finding the biomarker needle in the biological haystack is difficult and takes time, money, and lots of people. This is one of the reasons why there are only 20 FDA approved biomarkers for cancer (data from 2014). But just because it's difficult, doesn't mean it's impossible. Furthermore, this effort is necessary to improve healthcare and decrease healthcare costs in the future. It just might take a bit more time than we'd all like.
If you want to read more about the challenges and some of the solutions to biomarker discovery in cancer, take a look at this scientific article. Or read about some successes from right in our backyard at Arizona State University on identifying biomarkers for the early detection of ovarian cancer and breast cancer.
Dr. Cathy Seiler is the Program Manager for the tissue biorepository at St. Joseph's Hospital and Barrow Neurological Institute. She has her BA in Biochemistry and Molecular Biology from Boston University and PhD in the Biological Sciences from Cold Spring Harbor Laboratory. Her research and teaching focuses on genetics, cancer, and personalized medicine. Find her on Facebook at www.facebook.com/thingsitellmymom