New research led by a Carle Illinois College of Medicine student suggests sampling the genetic makeup of tumors in the liver could help identify the most effective cancer-fighting strategy. The studies focus on identifying genetic markers that could point the way to more targeted treatment for patients with hepatocellular carcinoma (HCC), an aggressive form of liver cancer. The research may be especially important for populations whose tumors show a limited response or come back after initial treatment.
HCC is the most common type of cancer that starts in the liver, accounting for about 75% of all cases. It can be hard to treat because patients’ response to treatment varies widely. When doctors suspect a patient has liver cancer, it’s standard practice to order diagnostic imaging such as MRI or CT scans to identify a tumor and determine how big the lesion has grown. But CI MED student Vish Vijayakumar suggests those methods may be missing information that’s crucial to choosing the best treatment for the patient.
“Most decisions to use locoregional therapies used to treat liver cancer tumors don’t take the biology of the tumor into account,” Vijayakumar explained. Locoregional therapies are minimally invasive image-guided treatments directed at the tumor site. “We propose that one of the ways that we can decide which therapeutics to use is from analyzing HCC biopsies,” he said.
Vijayakumar and his team tested their theory with patients whose tumors were inoperable. They sampled genetic material from HCC tumors before treatment and then used CT and MRI scans to measure treatment response three months after the patient underwent tumor-directed treatment. The team found significant differences in tumor response that correlated with the presence of certain genetic markers. “This study helps further the idea to other members of the liver cancer research community that studying the biology of liver cancer tumors is worthwhile and can help predict the response to locoregional therapies,” Vijayakumar said.
Additionally, the team’s work identifies markers that could be important in improving care for patients across ethnic and racial demographics. “We identified differences in gene expression between different populations. Studying these differences further can help delineate differences in tumor biology and evolution between different races and further develop better ways to treat HCC,” Vijayakumar said.
“Because our sample size was about 50 tumors with certain limitations in this study, we think that the markers we identified in this study can be targeted and studied in future research trials to help develop optimal treatment strategies in HCC,” Vijayakumar said. It could mean future patients diagnosed with liver cancer will receive more customized care. “The individual tumor profile could be better developed by pursuing biopsies in liver cancer patients to advance precision medicine approaches, or the ability to tailor therapeutics based on the biological make-up of a patient’s liver cancer tumor.”
In a separate study using liver tumors from pigs, Vijayakumar and his research team developed a genetic sequencing tool to study another obstacle to effective treatment: the biological variation within individual HCC tumors. “Our tool helped us study biopsies from five different regions of a single porcine liver cancer tumor. We found that there is significant diversity in the mutations present between the regions,” Vijayakumar said. “This [diversity] is important because we are finding that if even a small region of tumor resists treatment response, that can lead to recurrence of the tumor and repeated treatments.”
Vijayakumar presented the findings at the recent Swine in Biomedical Research Conference, in hopes of connecting with other researchers interested in advancing this field of research. “Our future work is going to start to build and characterize porcine liver cancer models with different gene mutations with the goal of personalized models to test therapeutics,” Vijayakumar said.
Collaborators on Vijayakumar’s research include University of Illinois Urbana-Champaign Professor Emeritus Lawrence Schook, the Edward William and Jane Marr Gutsgell Professor of Animal Sciences and Radiology; Professor Mohammed El-Kebir, from the Department of Computer Science at The Grainger College of Engineering; and Kyle Schachtschneider, PhD, Vice President of Research & Development at Sus Clinicals.
The study “Gene expression and DNA methylation patterns stratifying hepatocellular carcinoma tumors from patients by response to locoregional therapy (LRT),” published in the Journal of Vascular and Interventional Radiology, can be found here.