Revolutionizing Cancer Care With Genomic Testing

David L. Bartlett, MD

Thanks to advances in genomic testing, experts can now analyze hundreds of genes compared with just a few in the past, allowing for faster and more efficient identification of the right treatment for each individual patient.

According to David L. Bartlett, MD, genomic testing allows clinicians to target specific mutations within a tumor, which has led to an increase in effective therapies and improved patient outcomes. One emerging technique he highlighted was liquid biopsy, which analyzes circulating tumor DNA in the blood, eliminating the need for invasive biopsies.

Bartlett, chair of the Allegheny Health Network Cancer Institute in Pittsburgh, Pennsylvania, emphasized the impact of the growing role of genomic testing in various cancers, specifically in lung cancer where it is being used to guide treatment decisions. However, this is not the only space genomic testing is being used.

“Lung cancer is important, but we are also seeing it as important in colon cancer. It is also helping us define whether patients will respond to immunotherapy,” said Bartlett in an interview with Targeted Oncology^TM.

In the interview, Bartlett also explored the potential of next-generation sequencing (NGS), discussed ongoing research for cancer diagnosis and treatment, and highlighted the utilization and growing importance of genomic testing in cancer care.

Cancer detection and screening as a treatment for malignant cells with a biopsy or testing caused by carcinogens and genetics with a cancerous cell as an immunotherapy symbol: © freshidea - stock.adobe.com

Targeted Oncology: What are the benefits of genomic testing for patients with cancer?

Bartlett: Genomic testing is basically us looking at all the mutations that exist within a cancer. We biopsy the cancer, and then we sequence the cancer and identify the mutations associated with that cancer. This is extremely important for us to be able to target therapy to those specific mutations. While not every cancer has targeted therapy, we are seeing more cancers over time develop targeted therapies specific to mutations. Knowing those mutations upfront is extremely important for us.

How has the approach to genomic testing changed over the years?

Over the years, [we have seen] an explosion of our understanding of tumor genomics and what mutations exist within the tumor. What used to be a panel of 2 or 3 mutations that we would look for in a tumor, we are now up to greater than 500 genes that we regularly screen for known mutations that impact cancer specifically. The amount of genetic material that we assess for and then the number of mutations, and also the efficiency of doing that [has improved]. The original Cancer Genome Project and Human Genome Project took 13 years for a single sequence, which we can now do in a day, so the efficiency of our ability to analyze these mutations has improved over time.

What have been the most recent advances in genomic testing?

We continue to have great advances in terms of identifying targeted therapy and small molecules that can hit specific targets. We have over 100 now approved drugs for specific mutations within cancer. There has been an explosion of information with the first approved drug was imatinib [Gleevec] for a targeted mutation, and that was back in 2002.

The other specific advance is the ability to identify circulating tumor DNA. DNA in the blood, we can now analyze for the same mutations that we analyze in the tumor. We know tumors shed DNA into the blood, and we can identify the tumor mutations with a blood test. That is a huge advantage. It gets around us having to do biopsies, which can have a negative impact on patients. It also just makes it a little more easy and rapid for us to get the information that we need through a liquid biopsy. While that technology is evolving, and we are still trying to understand a little more about whether the liquid biopsy accurately reflects what the tumor biopsy is, I believe that the liquid biopsies will take over in the future and be a better representation of what's going on in the tumor.

What cancer types is genomic testing most frequently utilized in?

A lot of people would say any metastatic solid tumors should have a complete genomic profiling done at the diagnosis so that we can look for all possible targeted mutations, as well as availability for clinical trials as new drugs come on board. But where it becomes most important is in lung cancer. Lung cancer genomics defines the ability for us to start treatment for those lung cancer patients. We need to have that information as soon as possible. As I said, what used to take a long time, we can now get within just a couple of weeks of a full profile on that patient. Basically, that patient is waiting for that profile before they embark on treatment.

Lung cancer is important, but we are also seeing it as important in colon cancer. It is also helping us define whether patients will respond to immunotherapy. Immunotherapy can be a game changer for some of these patients, so we would like to know upfront if patients would be eligible for immunotherapy, as that could be transformative for them. So all cancers, but lung cancer being the most important right now.

Can you discuss NGS as a primary tool for genomic testing?

Next-generation sequencing is what we use now to sequence tumors. It is just a way that we can have very high throughput and rapid and efficient sequencing of the entire tumor genome. It is the technique that we use for rapid sequencing of tumors to identify the mutations.

Are there any strategies for using NGS and its clinical applications?

I think the strategy is still around what we need targeted gene mutation profiling for. Certain types of tumors, for instance, we might have different drugs that would treat a lung cancer mutation better than it would treat a colon cancer mutation, so we look at whether we should have some targeted profiles for different cancers, or should we just run the same profile of all known mutations in all cancers? It somewhat gets down to cost, expenses, insurance reimbursement and some complicated factors that may help direct how we do this in the future. But what we expect to happen is that every patient that has metastatic solid tumor will get NGS sequencing and identify all of the known tumor mutations associated with cancer. That way, we just have the most complete information on every patient that we are treating, and again, open it up to new drugs, new clinical trials, as well as existing immune therapies and other treatments.

What challenges do you think need to be further looked at?

Where we get interested is in looking at how these mutations might also be utilized to diagnose cancer, especially when we talk about liquid biopsy. So diagnosis and screening, using an NGS approach of some sort, is also an exciting aspect of this field moving forward. We know that DNA is leaked into the blood system constantly by tumors, even early tumors, so if we can use that as a way to screen cancers, using NGS sequenc[ing], identifying mutations specific to cancers, then not only can we identify whether a patient has cancer somewhere in their body, but also maybe pinpoint what cancer that is to direct further workup. I think where it gets exciting is if you think about using these technologies to screen for cancer earlier as well as to detect and follow patients who are being treated with cancer to know whether or not they're responding to treatment.

Are there any other ongoing research in this area or any other?

There is a lot of exciting research in terms of how [to make] the tests more sensitive to be able to identify more mutations and how you may be looking at other ways to analyze the DNA other than just sequencing that might predict different aspects of cancer and the presence of cancer. There is an enormous amount of exciting research that I think will be developed in the near future to help direct us more from a biomarker standpoint in cancer.