Tumor profiling model finds potential therapeutic agents for HCC

In a retrospective study, researchers used Caris Molecular Intelligence to identify molecular patterns and therapeutic options for hepatocellular carcinoma and presented the data at the 68th Annual Cancer Symposium of the Society of Surgical Oncology in Houston, according to a news release.

Caris Molecular Intelligence (Caris Life Sciences) is a tumor profiling service that includes gene sequencing, protein expression analysis and gene copy number analysis to show the molecular differences in HCC. The approach was used among 313 tumor samples of patients with HCC to describe molecular patterns and associations and also to identify potential therapeutic targets, according to the release.

“Patients with HCC have limited therapeutic options and there is little guidance for clinicians when weighing the next therapeutic steps for sorafenib-refractory disease,” Celina Ang, MD, researcher and assistant professor of medicine, department of hematology and medical oncology, Icahn School of Medicine at Mount Sinai Hospital, said in the release. “This data demonstrates how molecular profiling can reveal potential actionable targets in HCC to provide additional treatment options for patients.”

From the tumors, researchers found the tumor suppressor gene p53 (TP53) was mutated in 28% of all the samples. In addition, the TP53-mutated samples demonstrated higher expressions of topoisomerase 2A, thymidylate synthase and ribonucleotide reductase M1 (RRM1), indicating high rates of tumor growth and DNA synthesis, according to the release. Other frequently mutated genes found in the samples included the catenin beta 1 (CTNNB1) and BRCA2.

The findings suggest that anthracyclines, fluoropyrimidines and gemcitabine might benefit patients with TP53-mutated liver cancer.

The release further stated that 52% of the samples showed high expression levels of programmed cell death protein 1 (PD-1), and 80% showed low expression levels of thymidylate synthase (TS). Metastatic liver cancers (n = 105) exhibited significantly higher expression of PD-1 and lower TS than primary liver cancers (n = 209), suggesting the potential utility of anti-PD-1 immunotherapy in patients with metastatic liver cancer.

“Our observations of the molecular structure of hepatocellular carcinoma are generally consistent with the literature, showing few gene mutations and more protein alterations in these patients,” Sandeep K. Reddy, MD, chief medical officer at Caris Life Sciences, said in the release. “Therefore, a multiple technology approach to assess biomarkers should be considered, as a single technology approach, such as Next-Generation Sequencing only, may provide limited data to the treating oncologist. The data also suggests that [tyrosine kinase inhibitors], PD-1 and the PI3 kinase pathway inhibitors may benefit selected patients with liver cancer.”