Cancer patients are often encouraged to have DNA testing performed on their tumor. This type of testing can be helpful, but sometimes it leaves you with few actionable insights and indirect treatment suggestions.
But don’t worry, Cure-Hub developed a system that can help answer questions about drug targets in your tumor. Before we explain Cure-Hub’s solution, let us explain why mRNA gene signatures give you answers that are missed by DNA testing.
Different Cells, Different Genes, Different Actions
To best explain this section imagine looking at your reflection in a mirror. As you think about your facial features, focus on the color and shape of your eyes and nose.
Your body is made of many unique cells that do unique things. Some cells form parts of your eye and some form parts of your nose, which is why you have senses like vision and smell. Our variety of senses exists because we have different cells that use different genes to perform different functions.
Even though your cells do many different things, each cell has the same exact copy of your DNA. Your DNA has the instructions for all of your body’s processes, but cells in your eyeballs don’t use DNA instructions on how to ‘smell’ things.
This is because cells in your eyes express genes related to vision and the cells in your nose express genes related to smell. This means if we want to know what a cell is doing, we must look at gene expression and this requires measuring something called mRNA, not DNA.
What Is mRNA?
Analogies are great for introducing new concepts and we feel this is a great analogy to help introduce RNA:
Suppose an individual cell is like a factory that makes thousands of different widgets. Each widget represents a different gene product. Up in the foreman’s office is an instruction manual with directions for making every single widget, or gene product. That instruction manual represents DNA.
Only the factory boss can read the DNA instruction manual and when he wants a specific widget made he must write a message to the factory workers. The boss’ message is like mRNA and each time a certain widget is made, the boss must send another identical mRNA message.
Therefore, you can tell how much a specific widget, or gene product, is being made based on the number and content of mRNA messages being sent in the cellular factory.
In order to understand a cell’s behavior, we need to determine the number and contents of all of its mRNA messages. Reading the DNA instruction manual won’t tell us that information.
Collectively, all of a tumor’s mRNA messages are known as the gene signature. Healthy tissues also have a gene signature and we can compare them to tumor gene signatures.
Tumor Cell Gene Signature
Cancer cells take advantage of the DNA instruction manual to express genes that they aren’t supposed to express. This means a tumor has a unique gene signature.
Cancer cells specifically use genes that lead to tumor formation and maintenance. For example, they can use high amounts of genes that cause cell division, movement around the body, or immune inhibition.
When we determine the unique features of a tumor’s gene signature, we can look for the most active genes compared to adjacent normal tissue. Next, we cross reference those active genes against cancer drugs.
This can help make more accurate treatment decisions. Now we aren’t just guessing, we are using a rational decision-making system.
DNA Tests Don’t Tell You Immune System Involvement
Immunotherapy drugs like aPD-1 or aCTLA-4 are more likely to work if your immune system has pre-existing recognition of the tumor. Pre-existing recognition means that your immune system saw that the cancer cells were a problem, then marched to the tumor to try to do something about it.
The problem is your army of immune cells didn’t defeat the tumor. Maybe the tumor cells were ready and had their defenses up. Sometimes tumor cells defend themselves by using genes that prevent your immune system from doing its job.
But DNA testing won’t tell you the defense mechanisms that the tumor is using, you need to look at the gene signature to figure that out.
Remember that cells on both sides of this fight are also packing pretty identical instruction manuals, or DNA. However, testing tumor DNA doesn’t tell you which genes are actually being used. Determining the genes used in the tumor can however, tell us which immune cells are present because immune cells express certain genes that identify them as immune cells.
This means that we need to look at a tumor’s gene signature to determine the different players involved. Gene signatures can also tell us the genes that tumors use to keep your immune system at bay. This will help us understand the best immunotherapy options.
How Do We Test Gene Expression?
Some tests can simultaneously analyze the expression level for every gene in the genome. This type of test is called a gene array.
If we do a gene array on a whole piece of tumor the results will tell us the tumor’s gene signature. This can help determine how the tumor is defending against the immune system, if there are any immune cells present, and the ways the tumor is maintaining growth.
When we know this information, we are better prepared to select druggable targets for the tumor.
Medicine Hasn’t Caught Up To The Tech
Unfortunately, gene arrays aren’t clinically available. This means you can’t ask your doctor to test your whole tumor gene signature.
At Cure-Hub we figured out an indirect way to get around this problem.
In the research setting people use gene arrays on whole tumor samples all of the time. Researchers then deposit their entire gene array data sets onto publicly available databases at the National Institute of Health (NIH).
As of now there are hundreds of human tumor gene arrays for each tumor type on the NIH database. With that number of samples, we can create average gene signatures for each tumor type to try to determine the good drug target candidates.
The Cure-Hub Solution
Your team at Cure-Hub has extensive experience building systems that help you understand gene signatures. We are interested in using gene signatures to determine the best treatment options for any given tumor type.
For each tumor type we are harvesting hundreds of open source tumor gene arrays from the NIH database. We use the datasets to create average tumor signatures for each tumor type. This tells us the unique gene expression pattern for different types of cancer.
Next, we cross reference a tumor’s gene signature against a database of drugs that target specific genes. The end result is a list of drugs that target the most highly expressed genes in any given tumor type.
We believe that Cure-Hub is the first group to make gene signature and drug target information publicly available to cancer patients, physicians and researchers. Anyone can use this information to determine new treatment options, potential clinical trials and new drug targets.
We currently have a cool interactive chart of gene signatures for the first few cancer types. The chart can be found here.
If you want to know more about how we are harvesting gene array’s, read the page, here.
Check it out and be sure to send us an email if you have any questions!