Personalized Treatment for Subtypes of HCC Is the Way of the Future

Yujin Hoshida, MD, PhD

Many subtypes have been identified in hepatocellular carcinoma (HCC) over the last decade, and the use of new genomic technologies has made this possible. There is now research suggesting that there may be a potential link between how patients with different molecular subtypes of HCC may respond to different therapeutic options.

Despite the expanded knowledge regarding molecular subtypes in HCC, more research is necessary to identify what patients may respond best to certain treatments, such as immunotherapeutic agents and combinations. With improved understanding and knowledge from clinical trials, physicians can personalize treatment considerations for patients from specific subtypes of HCC.

In order to improve upon the current knowledge of subtypes in HCC and potentially links to response to therapy, researchers must work together with clinical trials to determine the subtypes most likely to respond to select therapies. By working together, this can be achieved most efficiently, an expert said at the 2020 HCC-TAG Conference.

In an interview with Targeted Oncology, Yujin Hoshida, MD, PhD, associate professor of internal medicine, University of Texas Southwestern Medical Center, discussed the next steps for improving upon the current understanding of HCC subtypes to improve responses and outcomes in patients with HCC.

TARGETED ONCOLOGY: Could you provide an overview of your presentation from the 2020 HCC TAG Conference?

Hoshida: We discussed the potential clinical utility of liver cancer subtypes, which has been mostly biological knowledge with no clinical utility so far, but a recent study suggested that some subset of liver cancer patients potentially respond to specific drugs. I think it is perfect timing to revisit HCC subtypes to learn if we can find something clinically useful, especially in terms of deciding which drug to give to each specific patient. We discussed what is known so far and the potential link with our recent clinical observation and how we could possibly utilize this concept in drug development and how we can apply this strategy clinically in real-life patients.

TARGETED ONCOLOGY: Could you elaborate on these subtypes of HCC?

Hoshida: Over the past decade, many people have tried to define the molecular subtypes of HCC. As newer genomic technologies emerge, everyone is trying the new technology, and each research team has identified different subtypes. We are accumulating knowledge, but we are gradually learning that each study is capturing something clonal. Everyone is describing it in their work, but they are capturing something clonal. That may be the place to start to link with specific drug therapies because this way of looking at liver cancer may be an efficient way to identify the potential specific drugs for a specific patient rather than chasing 1 single target at one at a time for each drug.

TARGETED ONCOLOGY: Would you like to expand on this potential link?

Hoshida: There are a few, which is likely to be considered under the concept of a subtype. We are still looking at the data to directly prove this concept because we don’t know what subtypes exists in the patients who are tested in those clinical trials. One way to move this concept forward would be to retrospectively analyze the archived patient specimens who have been enrolled to those clinical trials in an unbiased way so that we can explore lots of ideas and make sure we don’t miss any link with an existing subtype.

TARGETED ONCOLOGY: How do you see drug development moving forward in this space?

Hoshida: It is a joint effort, and that is the key factor. No single group can make the finding that is useful and influential to other people, so we need to work together. Oncologists and translational scientists should work together to move this forward most efficiently.

TARGETED ONCOLOGY: Is there anything else that is important to take away from the treatment landscape of HCC right now?

Hoshida: The 1 major and hot interest is immunotherapy. The other aspect of my session was we elaborated on the possibility of immunotherapy, which can be integrated into the concept of subtypes because as we know, some subtypes look more immune-reactive while others are not. Having accumulated the knowledge of subtypes may also inform how we can best utilize immunotherapy and combination therapy.

Other than those experiments though, many clinicians are actively discussing how to maximize the impact on the real patient survival and quality of life. It is a really exciting time. We as translational research scientists want to contribute to this.