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Dr Walko

5 Common Patient Questions about Molecular Tumor Profiling


Guest post by Christine Walko, PharmD, BCOP, FCCP
Clinical Pharmacogenomic Scientist, DeBartolo Family Personalized Medicine Institute
Chair, Clinical Genomic Action Committee
Lee Moffitt Cancer Center, Tampa, FL

Back in January, I initially discussed the concept and goals of a Molecular Tumor Board. The need for the Molecular Tumor Board grew out of the ability to assess the genetic “fingerprint” of an individual tumor and the challenge of how to translate this fingerprint into a clinical treatment decision for patients. As I previously discussed, the goal of the Molecular Tumor Board is to assess the results of the genetic tumor profile, determine the clinical relevance of each genetic alteration based on the patient’s characteristics and available literature and then communicate this information to the treating oncologist who will then discuss it with the patient. At the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, I presented in an Education Session entitled “Expediting the learning curve for applied cancer genetics.” My specific presentation was on “Using multidisciplinary tumor boards to augment the value of cancer sequencing.” The approach I took to this presentation was “5 things to consider when organizing a Molecular Tumor Board.” Following the end of my presentation, I was asked by a very enthusiastic and highly involved cancer research advocate about the role of patients in the process, specifically about how patients could be involved in optimizing tumor genetic discussions. This led me to consider common questions patients may ask about molecular tumor profiling.

1. What exactly are you looking for when you genetically profile my tumor?

When most people think about genetic testing, they may think about “germline” genetics or the genes that you inherited from your parents which are found in all the normal cells in your body.  With tumor genetic testing, we can see these types of genes since tumors evolve from normal healthy tissue. But tumors generally have a different genetic fingerprint that give some insight into why it became a cancer cell.  Basically, tumor genetic testing involves taking a piece of tumor (or blood or bone marrow if you have a blood tumor like a leukemia or multiple myeloma) and reverse engineering it to understand what went wrong in the cell and why it is growing so rapidly. Genetics cannot tell the full story on this – far from it – but it can give us clues as to what types of growth pathways are turned on. We know that genetic changes in molecular pathways are involved in the development of tumors as well as tumor survival, progression and spread to distant areas.  With our current technology, we can get a molecular fingerprint of the tumor. We can then look for oncogenes or tumor suppressor genes. An oncogene is a gene that when turned on by a mutation in that gene increases growth in cell (e.g. EGFR, KRAS, etc.); kind of like giving a car gas.  A tumor suppressor gene is a gene that when turned off by a mutation or other change increases growth in a cell (e.g. TP53 or RB).  Tumor suppressor inactivating mutations are like cutting the brakes on a car. Tumor genetic testing can look for a select number of mutations (most commonly up to a few hundred) or even sequence the whole tumor. What we look for are mutations in oncogenes or tumor suppressor genes that we can use treatments to target and block growth pathways turned on by these mutations.  

2. Do you always find something?

A better question is, “Do you always find something useful?” and the answer is unfortunately no. This is where the challenge of defining whether a genetic change is “clinically actionable” comes in. A clinically actionable change is a genetic alteration that predicts response to a particular therapy or a genetic alteration that provides diagnostic or prognostic information about the cancer. The chance of finding an actionable mutation depends upon the type of cancer and the number of genes being assessed by the laboratory assay. Once the results from the molecular test are back, your medical team and sometimes a Molecular Tumor Board will look at the available data to support which treatment recommendations may be most helpful. 

3. I have a report from a genetic profiling company. How can I narrow down the treatment options?

Ideally, this should be done in discussion with your primary treating oncologist. Depending on what laboratory ran the genetic test, the results can be reported differently and often include options that are not all that reasonable for most patients. Some things to consider and discuss with your doctor include whether you want to participate in a clinical trial and if so, what type. Clinical trials are the best way to get new therapies, especially new therapies that may target genetic changes in the tumor. But clinical trials sometimes have limitations. You have to be able to travel to the clinical trial site regularly for visits and you have to meet all the inclusion and exclusion criteria for the trial. Some trials require that you have a certain tumor genetic variation or type of cancer, where others may not. Sometimes, there is an FDA approved drug that is available and blocks a growth pathway that is turned on in your tumor. If the drug is FDA approved in your tumor type, then this may be an alternative to a clinical trial. However, what is more common is the availability of an FDA approved drug for a tumor type or situation different than what you may have. This is known as “off label” therapy.   

4. Based on the genetic profile results, I may qualify for “off label” therapy. What does that mean?

When drugs are FDA approved, the drug company that owns that drug submits everything that is known about the drug to the FDA. This includes large clinical trials that usually compare the drug to standard of care in a particular disease state. When the drug is officially approved, the approval will state the specific dosing schedule and patient population for which it is approved among lots of other safety information. These patient populations can be very specific such as “advanced non-small cell lung cancer patients with adenocarcinoma who have progressed on a prior cisplatin-based chemotherapy regimen.” Insurance companies use this approval information to decide for whom they will pay for the drug. Using a drug off label essentially means using the FDA approved drug for a different indication or patient population than for what it was approved. Generally when an off label drug is recommended, there is some clinical data to support it is helpful and safe in your type of cancer but perhaps not enough data for the company to submit it to the FDA for your specific indication. Whether your insurance company will pay for the drug depends on several factors including the specific drug, your type of cancer, what information is available in your type of cancer and the specific insurance company’s policy. Most times, the prescription is initially rejected by the insurance company but through an appeal process can be obtained. This appeal process typically takes 2 weeks and is explained on the rejection notice from the insurance company. 

5. Does insurance pay for the test?

Insurance companies do pay for many of the tests but not all. This depends on what type of cancer you have, what state you live in and what type of insurance you have. It is ALWAYS a good idea to ask this question to your doctor. Some tests are done at the cancer center where you may be getting treated while others may be sent out to commercial laboratories. These commercial laboratories may have resources to help with getting insurance company reimbursement but sometimes patients get expensive bills (a typical molecular test that looks at about 600 genes costs about $6000-7000) so it is always a good idea to check.

There are many other questions people ask about molecular tumor results and I am happy to answer any general questions you may have. Please feel free to email me at or post your comment below since others may have the same question.


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Common EGFR Analytical Techniques

(Click to enlarge)

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(click to enlarge)

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mTOR Mechanism MOA (click to enlarge)

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