Evolving Landscape of Genetic Testing in Oncology

Louise Morrell, MD

The use of genetic testing in oncology has expanded in recent years, and there has been a transformative impact of understanding DNA in cancer. Identifying genetic abnormalities in cancer cells, characterizing tumors, and using molecular markers for targeted therapies can make significant differences in creating treatment plans.

Louise Morrell, MD, emphasized the ongoing advancements in technology, making genetic testing more accessible and affordable. Despite improvements, challenges exist in obtaining sufficient tissue for testing, requiring diverse biopsy approaches. The integration of multidisciplinary efforts, including pathologists, molecular doctors, geneticists, and radiologists, aims to apply these advances in patient care.

In an interview with Targeted Oncology^TM, Morrell, medical oncologist medical director of the Lynn Cancer Institute, Boca Raton Regional Hospital, Baptist Health South Florida, discussed the landscape of genetic testing in oncology and the latest advancements in the field.

Targeted Oncology: What is the current landscape of genetic testing in oncology?

Morrell: Several things that have transformed the cancer field, all the way from diagnosis, prevention, and treatment outcomes, to what we have learned about DNA. There are 2 things that I think about when it comes to DNA and cancer. What makes a cancer malignant is that its DNA has changed. Essentially every cell in the body has the same DNA except for the cancer cell. Then those changes allow it to grow, to spread, to invade. We always know that every cancer cell has DNA alterations. Then when we talk about inherited cancer, we think about genes that we inherited, so every cell in our body has those changes that make us susceptible to cancer.

The reason this is important, and why it has been so transformative, falls into 2 separate categories, even though they overlap. First of all, the area of treatment, prognosis, and understanding the disease, and even monitoring cancers. This has been a huge breakthrough because we can identify the genetic abnormalities in the cancer cells characterize that cancer. We all know that lung cancer is all 1 cancer. Everyone wondered, why do some people do so poorly, and some people do well? Now we have a lot of information. It is standard to [test for] what are called molecular markers, which effectively are reflections of the genetics and of that tumor. Then, [we can] target the therapies and direct therapy for that. Lung cancer was the first area that completely transformed care. Everybody that has lung cancer has to have genetic testing of the tumor molecular markers to determine what the treatment should be. It's had a huge impact.

Every other cancer has some impact from that in terms of how we target therapy. The fewer treatments we had, the more impact this has been. Things like melanoma and pancreatic cancer had huge impacts. Now it has made its way into some areas of breast cancer, glioblastoma, etc. Our ability to characterize the cell, find out the key drivers of cancer, and then find a medication that is targeted has been the result of last 30, 40 years of lab [work] that resulted in this breakthrough. That is continuing to take place.

What are some of the barriers of genetic testing?

[For testing], we need to do is get fragments of DNA, or an entire strand of DNA, or the whole exome. There are all kinds of things [one] can test, but [we are] looking for the DNA particles which are living inside the nucleus of a cell. Every cell in our body has DNA. We can measure what you inherited. We do that primarily through the DNA that we find in the white [blood] cell. The white cell can either be found in the blood or in the saliva. We can determine if you have a BRCA gene, or one of the inherited cancer genes, through either saliva testing or through blood testing. So [it’s] simple to do in terms of collecting a sample from the patient.

On the lab side, there has been an enormous change in technology and efficiency. I explain to my patients all the time that the pendulum has gone from $4,000 for a single gene in 2 months to $250 for all cancer genes in 2-3 weeks. Now, availability allows us to study and to be able to offer this testing to a variety of patients and with a much lower threshold.

As a result, we are learning more about it. In the cancer world, the abnormalities are in the cancer cells themselves. Most of the time, you need the cancer tissue to do it. That is where sometimes it can be a little more challenging, because in the past, we could just do a little needle biopsy or [take] a little specimen, and you could diagnose the cancer. But now if you want to do these kinds of molecular studies, it may not be an adequate amount of tissue. [We] might have to do a different kind of biopsy or go back and do another biopsy.

Those DNA changes in the cancer can change over time. In addition to that, doing it from the tissue, another breakthrough is again, our ability to test DNA itself. We have fragments of DNA circulating in our bloodstream. We talk about not just circulating tumor cells that can be tested but look for certain fragments of DNA. In that case, [we] have to know what [we’re] looking for. We have to know, [we are] looking for this fragment and need to know if the person has that. But [we] can use that to monitor how the patient's responding or whether [we] expect them to be sensitive to a treatment.

What are some advancements in the field?

This is a profoundly exciting time for us. Part of the reason it is so profoundly exciting is because a lot a lot of lab research happened for many years. We saw that in [the] COVID[-19 pandemic] why were we able to explore this idea of going for RNA vaccines was because the technology had been advanced in other fields as well. It was a common technology so the ability in the laboratory to study these things has now become very vast. That makes it more widely available [and] that makes it more possible for us to investigate new treatments and to try new treatments.

Here is where I would explore the concept of artificial intelligence [AI]. AI is an intimidating word, I would say. If we change it to computer-assisted, we would probably be less in awe of it, because [AI] is just a progression of computer-assisted work. The whole advantage in computer-assisted work or AI is the ability to really go through so much huge data. DNA is an example of that. We have 6 billion DNA particles in every cell in our body. Now we have cancers that are not just 1 cancer, but can be hundreds of different cancers, with hundreds of different DNA patterns, and the ability to harness the data assessment. The ease of accessing data from patients, I think, is where the next step is going to be incredibly important for clinical implications.

What we are trying to do is remind ourselves that everything we have done, and every advancement we have made, number 1, we want to make it available to our patients. We are working as a team all the time with our pathologists, with our molecular doctors, with the geneticists, with the radiologists, with the team, so that we are certain to be applying all these advances to our patients. The second is to realize that everything we have in terms of advancements is because people before had done research, and so we must continue that we must deploy every opportunity to collect research. I'm excited about the different applications that can be possible and about being in a setting that is taking care of people and at the same time advancing research.

The main thing is that communicating with patients is the key. There is such a vast amount of information out there. As we all know, in every area, there is a vast amount of misinformation. That is why we are here. We have the time; we want to use our time to communicate and to make sure that the [patient] can completely understand what they're going through and what our expectations are and get their questions answered from people who are really dedicated: the physicians and [clinicians].