University of Pittsburgh scientists have identified gene signature panels to allow clinicians to identify patients with hepatocellular carcinoma (HCC) who are unlikely to respond to immunotherapy (IO). Using genomic analysis of either a solid or liquid biopsy it is possible to predict patients with mutations of the gene encoding b-catenin, identifying those who may be resistant to IO. This screening tool could aid clinical decisions around treatment decisions.
Description
HCC is the third-leading cause of cancer-related deaths worldwide. Amongst HCC patients, around one third have a mutation in CTNNB1, the gene encoding -catenin, and do not respond to IO. There is an urgent need to identify treatment for this cohort of patients. 13-gene and 10-gene panels have been developed to accurately predict CTNNB1-mutation and IO resistance which could allow researchers to develop precision treatments for these patients through molecular phenotyping clinical trial participants. This novel panel could, with time, dramatically improve the lives of people with HCC who are unsuitable for IO.
Applications
- Hepatocellular carcinoma
- Melanoma
- Colorectal cancer
Advantages
While advancements in immunotherapy have improved, treatment options for HCC patients with CTNNB1 mutations do not respond to IO. Time can be wasted on a futile treatment and patients may experience unnecessary harm. There is also a need to develop treatment for these patients.
Gene signatures can be used to identify mutations in -catenin and those patients less likely to respond to IO. Two panels, based on 13-genes and 10-genes have been developed. These could be used to stratify HCC patients, identify subsets of CTNNB1-mutant patients and those who may need more personalized treatment. Additionally, these panels may identify individuals who might be targeted in clinical trials to develop anti--catenin therapies for patients with CTNNB1 mutations.
Invention Readiness
Using humanized animal models of HCC, a mutated -catenin gene signature (MGBS) was identified. Two panels, a 13-gene and 10-gene panel were found to accurately predict CTNNB1-mutation status with AUC of 0.90–0.94. The 10-gene panel was trialed on a small cohort of HCC patients (n=17) and was shown to predict immunotherapy response with AUC of 0.78. This high level of predictability demonstrates promise for use in clinical and research settings.
IP Status
Patent pending
