Biomarker testing can open the door to additional, personalized treatment options, including clinical trials.
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Get the Right Tests & Find the Right Treatment for Cholangiocarcinoma
Biomarker testing can open the door to additional, personalized treatment options, including clinical trials.
If you’ve been diagnosed with cholangiocarcinoma, it is important that you and your doctor get as much information as possible about your tumour. Knowing your tumour’s biomarkers will help you both to make important decisions about your treatment.
“Thank goodness for research! Biomarker testing, also known as molecular profiling, has literally been a life-saver for me. Identifying my mutations opened up clinical trial treatment options. I am currently enrolled in a clinical trial and it has given me hope and life!”
What are biomarkers?
Your body is made up of different types of cells. You can think of each cell as a little factory that produces all sorts of molecules that keep the factory running smoothly. Each type of cell produces a unique set of molecules, called a molecular “signature”. This signature helps to identify each cell and its activities.
A biomarker is any molecule that can be measured in tumor tissue, blood, or other bodily fluids.
The term “biomarker” is short for “biological marker”. These markers provide a way for your doctor to monitor whether your body is operating normally or if there are signs of a disease or other condition.
When you have a routine blood test, your laboratory report lists a variety of biomarkers, like your thyroid hormone levels, glucose level, and red and white blood cell counts. This lets your doctor see how your body is functioning. It can also tell your doctor how you are responding to a medication.
What are cancer biomarkers?
Cancer cells were once healthy cells. Damaged genes caused the cells to go rogue. These rogue cells quickly multiply, forming a tumor that crowds out healthy cells. Cancer cells can “go rogue” in many different ways. If we took a close look at the tumor cells from three people with cholangiocarcinoma, we would likely find that different molecules are driving each of their tumors.
The term “cancer biomarkers” refers to molecules that are produced either by tumor cells or by other cells in the body reacting to a tumor. You might also hear them called “tumor markers” or “driver mutations”.
Cancer biomarkers can take several forms
Inside each of your cells is your DNA, which contains thousands of genes. Each gene provides the recipe for how to assemble a specific protein to help the cell function. If any of the instructions for building the protein are damaged, the protein that gets made will be faulty.
Damaged genes are said to be “mutated”. Mutations can be inherited or acquired.
- Inherited mutations are present in all of your cells. They are passed down through generations and can affect your risk for getting certain kinds of cancer. Testing for inherited mutations is called “genetic testing”. This is done mainly for risk assessment, often for those who do not have cancer.
- Acquired mutations are only present in tumor cells and are identified through biomarker testing. Knowing these biomarkers is helpful in making treatment decisions. Learn more.
Proteins are made by both healthy and cancerous cells. But cancer cells often produce too much of a protein or an abnormal protein. This can be detected through biomarker testing.
How are cancer biomarkers used?
Cancer biomarkers may be diagnostic, prognostic, or predictive. They all offer important clues that can help direct your care.
- Diagnostic biomarkers can tell you and your doctor whether you have cancer and help determine the type and form of your cancer.
- Prognostic biomarkers help to tell you how likely a cancer is to come back or progress. They can also forecast how you are likely to do, with or without therapy.
- Predictive biomarkers can help to identify which therapies might work for your particular tumor and which might be wrong for you. These treatments may be:
Biomarkers can also provide information that leads to
- FDA-approved (Australian Approved) therapies for cholangiocarcinoma,
- A therapy already approved to treat another cancer that is being studied in a clinical trial to see if it is effective in cholangiocarcinoma, or
- A therapy still in development that is being studied in a clinical trial.
Why do biomarkers matter for people with cholangiocarcinoma?
To date, researchers have discovered that there are many biomarkers associated with cholangiocarcinoma. Each person with cholangiocarcinoma has some of these biomarkers.
Many of the biomarkers seen in cholangiocarcinoma are also seen in other types of cancer. That is especially important for cholangiocarcinoma patients because some of these other cancers have treatments that may also work in cholangiocarcinoma. In fact, there are many clinical trials going on that are studying the potential effects of these treatments on cholangiocarcinoma patients who have certain biomarkers.
That’s why your biomarkers matter!
More than 50% of patients with cholangiocarcinoma have at least one biomarker that can be treated with a known therapy. We call these biomarkers “actionable”.
Knowing which biomarkers are driving your individual tumor can help you and your doctor decide the best way to treat your cancer. It can also open the door to newer drugs and clinical trials that are only available to patients with specific biomarkers.
Which biomarkers matter in cholangiocarcinoma?
The biomarkers driving your cancer may determine the type of treatment you are offered.
Targeted therapies focus on cells with a specific mutation, while minimizing harm to healthy cells.
Having at least one of the following biomarkers may make you eligible for treatment with an FDA-approved targeted therapy:
- FGFR2 fusions*
- NTRK fusions*
Other biomarkers may make you eligible for a clinical trial for a targeted therapy that is either still in development or already approved to treat another cancer.
* Gene fusions occur when a part of one gene attaches to part of another gene.
Sidney Kimmel Comprehensive Cancer Center
John Hopkins University
Immunotherapies use the power of your own immune system to treat your cancer.
Having any of the following biomarkers may make you eligible for treatment with an immunotherapy:
- Microsatellite Instability/Mismatch Repair deficiency (MSI/dMMR)
- High Tumor Mutational Burden (TMB-high)
How can I find out my tumour’s biomarkers?
Biomarker testing will tell you and your doctor about your tumor’s biomarkers. You might also hear it called “genomic testing”, “tumor testing” or “molecular profiling”.
There are different kinds of biomarker tests that will look only for specific biomarkers. To get a complete picture of the mutations or proteins that may be fueling (driving) your tumors growth, ask your doctor for Comprehensive Biomarker Testing.
There are 2 types of tests that are ordered
3-5 day cost-effective local laboratory test.
IHC is a common application of immunostaining. It involves the process of selectively identifying proteins in cells of a tissue section. IHC takes its name from the roots “immuno”, in reference to antibodies used in the procedure, and “histo”, meaning tissue.
Immunohistochemical staining is widely used in the diagnosis of abnormal cells such as those found in cancerous tumors. Specific molecular markers are characteristic of particular cellular events such as the proliferation of unrepaired DNA mistakes (mutations) or cell death (apoptosis).
The tissue sample is stained to highlight the presence of known biomarkers that relate to current clinical trials, immunotherapy, or targeted treatments. IHC tests can reveal whether checkpoint inhibitor treatments are a potential treatment option. PD-L1 expression and also identify proteins absent in the tumor sample, indicating that one of the Lynch syndrome genes might not be working properly. Lynch syndrome mutations affect whether the MLHL, MSH2, MSH6, and PMS2 proteins are made and located in the correct place, this also points to a MSi status.
Ref Immunohistochemistry screening + Applications of immunohistochemistry
Molecular (Genomic) Profiling:
Also known as…
NGS -Next Generation Sequencing.
4-6 week specialist NGS laboratory facility.
Most often it will be you the patient that will need to insist on having this test carried out.
Genomic Profiling looks at the whole composition of a tumour including your inherited (germline/genetics) and any acquired (somatic) influences. Somatic mutations are changes to your DNA that happen after conception to cells other than the egg and sperm, ie acquired or influenced after you were born. Click this link to learn more about the differences
- IHC test results are also included within a full Molecular (Genomic) Profiling.
- The reason you or your doctor would order an IHC test is for its speed in providing important information that could provide early options that match current clinical trials. (Targeted or Immunotherapy)
- You can have both tests (Ideally) but ensure that enough tissue sample (Biopsy) has been obtained to do both. In fact enough for further retesting is very advisable.
- You will need to ensure that you ask for the specific biomarkers mentioned on this page ie PD-L1, MSi etc
Don’t confuse genomic testing with genetic testing.
Genomic Profiling/testing checks your tumor cell’s whole molecular composition and looks for known biomarkers that can reveal what mutations (DNA mistakes) are present in the tissue sample being examined. These mutations are also described as your cancer’s mutational drivers.
Genetic testing is done using a sample of blood, urine, saliva, hair, amniotic, or other body fluid, to test for inherited mutations from your parents that could increase your risk for certain types of cancer.
As a Newly Diagnosed Patient, you do not know what you do not know.
The CCA Patient Toolkit is a “Precision Health Literacy” resource specifically developed for patients diagnosed with bile duct cancer. The Toolkit helps you know what you must know in the order you must know it. View the CCA Patient Toolkit
Biomarker testing requires a sample of your tumor tissue, usually collected via a biopsy. So if you’re having a biopsy, ask your doctor to collect enough tissue for biomarker testing as well. The tissue is then sent to a laboratory to find out which biomarkers may be responsible for your cancer.
This testing identifies any markers that can be targeted with current therapies as well as markers for which there may not yet be approved treatments; that way, if a new treatment becomes available down the road, your biomarker report could make you eligible for that therapy.
It’s a good idea to ask for a copy of the report for your own medical records.
When should I get biomarker testing?
Ideally, you want biomarker testing performed when you’re first being diagnosed with cholangiocarcinoma so you and your doctor will know all of your treatment options.
If you are having a biopsy because cancer is suspected:
- Tell your doctor you are interested in biomarker testing and ask that they collect enough tissue.
If you’ve already had a biopsy:
- Ask whether your tumor was tested for biomarkers.
- If it wasn’t: Ask whether biomarker testing can be conducted with the sample that was taken; that way you won’t need a second biopsy.
- If it was: Ask whether you qualify for any targeted therapies, immunotherapies, or clinical trials. Also be sure to ask for a copy of the report!
The Cholangiocarcinoma Foundation (UAS) has a list of clinical trials open to those with cholangiocarcinoma.
Over time, if a therapy stops working or your cancer comes back, that may mean that your tumor cells have evolved and developed new mutations. At that point, ask your doctor about having a second biomarker test. That may reveal new biomarkers that could be targeted.
Does insurance cover biomarker testing?
Recognising the value of biomarker testing for cholangiocarcinoma, many good insurance companies are beginning to cover this testing, so please check this directly with your insurance company.
What if my doctor doesn’t think I need biomarker testing?
Tell your doctor you want to know your biomarkers so you will both know all of your treatment options.