Fibrolamellar Cancer Foundation

The oncogenic fusion protein DNAJB1-PRKACA can be specifically targeted by peptide-based immunotherapy in fibrolamellar hepatocellular carcinoma

This article describes work conducted at the University Hospital Tübingen on the creation of a therapeutic peptide vaccine for fibrolamellar carcinoma. Using FLC’s characteristic DNAJB1-PRKACA fusion protein, they designed a personalized peptide vaccine using fragments of that DNAJB1-PRKACA protein and administered it to a patient with FLC. The patient, a recipient of a liver transplant, …

Histologic type predicts disparate outcomes in pediatric hepatocellular neoplasms: A Pediatric Surgical Oncology Research Collaborative study

In this study, researchers reviewed the detailed medical records of 262 patients under age 20 diagnosed with liver cancers, assembled from 19 different hospitals and covering the years 1990 to 2017. This represents the richest available source of data on these pediatric liver cancers. They found that 119 (45%) of the tumors had been classified …

Multi-omic analysis of microRNA-mediated regulation reveals a proliferative axis involving miR-10b in fibrolamellar carcinoma

Nearly all FLC tumors carry the fusion gene DNAJB1-PRKACA and the expressed protein chimera DNAJ-PKAc which is believed to be the driver of FLC formation. However, to identify potential new therapies for FLC, it is important to understand the specific mechanisms that drive the progression of the disease. In a previous study, the Sethupathy lab …

Clinical and demographic predictors of survival for fibrolamellar carcinoma patients—A patient community, registry‐based study

This study looked for associations between demographic, clinical factors and overall survival using data from the Fibrolamellar Registry. Several key findings emerged: In conclusion, while this study provides insights into factors associated with survival in FLC patients, further research is needed to better understand this rare cancer. The full text of the publication can be …

Fibrolamellar carcinoma transcriptomic-based treatment prediction: complete response after nivolumab and ipilimumab

This paper discusses a case study of a patient in her mid 30s whose FLC had recurred and persisted despite resection and multiple lines of treatment, including use of an immune checkpoint inhibitor (atezolizumab – an anti-PD-L1 agent). Following molecular profiling of her tumor and computational analysis of the tumor’s transcriptome (RNA), a combination of …

β-catenin cancer–enhancing genomic regions axis is involved in the development of fibrolamellar hepatocellular carcinoma

The purpose of this study was to examine the role of human genomic regions, called cancer-enhancing genomic regions or aggressive liver cancer domains (CEGRs/ALCDs), in the development of FLC. In previous investigations of the mutation-independent pathways of pediatric liver cancer hepatoblastoma, researchers identified CEGRs/ALCDs that control the expression of a group of cancer-causing genes. In …

Targeting BCL-XL in fibrolamellar hepatocellular carcinoma

Fibrolamellar carcinoma (FLC) is a cancer that doesn’t respond well to current treatments. In past research, the Rockefeller University team conducted a broad-based, small-molecule drug screen to identify potential drug candidates to use against FLC. That effort identified several potential drugs including napabucasin, panobinostat, irinotecan (a topoisomerase I inhibitor), and navitoclax (an inhibitor of the …

DNAJB1-PRKACA in HEK293T cells induces LINC00473 overexpression that depends on PKA signaling

While FLC in almost all patients is caused by the DNAJB1-PRKACA gene fusion, the mechanism by which that fusion causes the cancer is still unclear. In order to get insight into that question, this team engineered the DNAJB1-PRKACADP fusion gene into “immortalized” liver cells and measured the impact that the change had on the functions …

Clinical Outcomes in Fibrolamellar Hepatocellular Carcinoma Treated with Immune Checkpoint Inhibitors

Although immune checkpoint inhibitors (ICIs) are becoming the standard of care in some types of cancers, few studies have looked at the safety and efficacy of ICIs for treating FLC. This multicenter, retrospective analysis aimed to determine if treatment with ICIs could be helpful for FLC patients. Patient data included in this study was identified …