In the past, doctors have noticed a trend in hepatocellular carcinoma (HCC). More specifically, research has shown that HCC can grow resistant to certain drugs. This makes it more difficult to treat and, as a result, contributes to worse patient outcomes. Determining ways to overcome drug resistance can significantly alter the treatment landscape.
Multiple forms of HCC treatment exist: chemotherapy, cryoablation, surgery, radiation, percutaneous ethanol injection, and liver transplants in severe cases. However, there are a subset of patients who cannot undergo surgical resection. Lenvatinib is often used in these cases.
Lenvatinib, a targeted treatment against VEGFR1, VEGFR2, and VEGFR3 kinases, has proven effective in treating various forms of cancer. Yet many people with HCC do not respond well to treatment. But why is that? It seems that genetics may play a role. A news release shared by UT Southwestern Medical Center explains that researchers discovered genetic markers that could predict drug resistance to lenvatinib.
The Challenge of Treatment Resistance
To begin this retrospective study, the research team examined circulating tumor DNA from 46 people with HCC prior to, during, and following treatment. Of these individuals, 30 (65%) were given immunotherapy and 16 (35%) were given lenvatinib. They found that EGFR and ERBB2 mutations increased in people treated with lenvatinib. Since EGFR and ERBB2 mutations have been associated with tumor growth and various forms of cancer, this finding interested researchers. So, they analyzed data from an additional 227 people with HCC.
Again, they found a relationship between HCC outcomes and EGFR and ERBB2 mutations. First, people whose tumors had these mutations did not survive as long as people without the mutations. Lenvatinib also shrank tumors, or stopped disease progression, in 62.5% of individuals without these mutations; only 20% of people with these mutations had the same result. Finally, the research team branched out once more, examining data from 1,616 individuals. They found EGFR and/or ERBB2 mutations in around 11% of people living with HCC.
More research is needed to understand how these mutations may contribute to HCC drug resistance and whether these results can be validated. However, they do suggest that identifying or providing alternate treatments to certain patients could overcome treatment issues.
Findings from this research can be found in Gastroenterology.
About Hepatocellular Carcinoma (HCC)
While hepatocellular carcinoma is rare, it is also considered the most common form of primary liver cancer (or cancer that manifests in the liver). Having hepatitis B or C, drinking alcohol heavily, being obese, having diabetes, or having pre-existing liver conditions all increase the risk of developing HCC. Early identification and treatment can improve survival. Unfortunately, this can be tough as some people with this cancer don’t show any symptoms in early stages. When symptoms appear, they may include:
- Appetite loss
- Unintentional weight loss
- Fatigue and general weakness
- Upper right abdominal pain or heaviness
- Abdominal bloating and distention
- Nausea and vomiting
- Pale bowel movements and dark urine
