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Molecular Testing Advancements Leading Field of GI Cancers

Danielle Bucco
Published: Tuesday, Dec 26, 2017

 Shirley Michelle Shiller, DO
Shirley Michelle Shiller, DO
With the advent of next-generation sequencing and novel technologies, the understanding of the molecular alterations in gastrointestinal (GI) cancers has significantly improved.

In addition, the development of the ASCO guidelines for GI cancers has given oncologists a baseline of treatment options when a mutation or molecular alteration is identified in an individual tumor.

For example, ASCO has updated its provisional clinical opinion on testing patients with metastatic colorectal cancer (CRC) for KRAS mutations to determine whether they should receive anti-EGFR monoclonal antibody as treatment.1

“It is important that the guidelines are followed so that, ideally, every patient has that fundamental baseline treatment,” explains Shirley Michelle Shiller, DO.

In an interview during the 2017 OncLive® State of the Science SummitTM on Gastrointestinal Cancers, Shiller, a pathologist at Baylor Scott and White Health, discussed progress with precision medicine for patients with gastrointestinal cancers.

OncLive: Please provide an overview of your presentation.

Shiller: I discussed the recent guidelines and recommendations, which were a collaborative effort between ASCO and various pathology organizations to ensure that we are streamlining testing.

Additionally, I spoke about liquid biopsies and expanded testing, as well as immuno-oncology therapy that is newer but also very effective. I gave hints about some technology to look forward to in the future.

Can you discuss some of the highlights of these guidelines?

The guidelines are intended to help direct clinicians, especially those who may be in more remote areas, to have a baseline as to what any patient should receive in terms of treatment. Some alterations, such as KRAS mutations, indicate that a patient would not respond to select therapies and therefore helps to direct the therapy to a more meaningful and efficacious treatment for the patient.

Can you discuss the current role of liquid biopsies?

That is one of the emerging technologies. It has met some clinical utility, but it has been utilized more in the lung cancer space thus far. We are still learning a lot with it. A liquid biopsy could be from plasma or urine, although urine is the least understood. The plasma-based testing we know the most about is in the lung cancer space, but it has opportunity in colon cancer so some people are starting to use it there. 

The detection rate is lower in plasma versus in a solid tumor and, at this time, that is largely based on our experience. We have more experience testing solid tumors. When you move into the liquid space, there are some sensitivity issues that we are working on, as well as the other variables that you cannot control as much. For example, when you draw blood, it is not certain that the tumor is shedding at that time or that the mutations that you are hoping to detect are shedding enough of a quantity to be detected.

What role will liquid biopsies play in the future of this treatment landscape?

I am certain that it will play a role in all cancers. Lung cancer has the head start, although the diagnosis of leukemia is done on bone marrow specimens and blood. We are now applying it to solid tumors, but it is different because that solid tumor does not exist in the bloodstream. Those are the challenges, but we will get better with time.

Ultimately, we will understand how to utilize the information that we are receiving in terms of an initial diagnosis on the tumor. The histologic diagnosis may not even matter in the long term, but what might be more relevant are the biomarkers. Once we know what we are looking to monitor, then we can watch those patterns prior to a patient presenting with a recurrence.

Looking to the future, there are some [pharmaceutical] companies that are hoping to detect cancer before an actual lesion is even present. That is very far [off] in the research future but I believe that will become reality at some point. 

What impact has precision medicine had on the treatment landscape thus far for these patients?

Ultimately, there are several layers. First and foremost, we are having growing pains because some of the testing can be more expensive than a routine blood test or chemistries. However, the information is very important if you are contemplating what therapy to give patients. We are in a power struggle with third-party pairs as we get our feet on the ground to demonstrate the benefit of the test and how that saves money downstream in terms of not delivering ineffective therapy. Therefore, the patient is getting therapy that is more specifically targeted to their actual cancer, which is the essence of precision medicine.


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