Fibrolamellar Cancer Foundation

Identification of Novel Therapeutic Targets for Fibrolamellar Carcinoma Using Patient Derived Xenografts and Direct from Patient Screening

This publication describes the results of the first large scale screening of known drugs and compounds for their effectiveness against FLC. It identified six new PDX lines derived by direct implantation of tumor specimens, both from the liver (one primary and one recurrent tumor) and metastases. These facilitated the first reported large-scale screening of compounds …

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 …

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 …

Oncogenic Addiction of Fibrolamellar Hepatocellular Carcinoma to the Fusion Kinase DNAJB1-PRKACA

Based on another study from the Simon lab, we have known that a gene fusion called DNAJB1-PRKACA produced a mutated protein kinase A (PKA) that causes 99% of cases of fibrolamellar carcinoma. In this study, the researchers found that this gene is not only important for the growth of FLC tumors but also that blocking …

Defining incidence and complications of fibrolamellar liver cancer through tiered computational analysis of clinical data

Rare diseases like fibrolamellar are often poorly understood because of the difficulty in assembling accurate patient data and the lack of ICD billing codes specific to the disease. The most cited study of the incidence of FLC in the US, using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program, reports …

Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma

In this study, the researchers used a method called mass spectrometry to study the proteins and metabolites inside FLC tumors and compared them to normal liver tissue. They found that the proteins in FLC tumors are different from those in healthy liver tissue, which could explain why FLC cells react differently to certain drugs and …

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, …

A framework for fibrolamellar carcinoma research and clinical trials

This article, published in Nature Reviews Gastroenterology & Hepatology, summarizes the key advances made in understanding the disease since the 2014 discovery that nearly all FLC tumors contain the DNAJB1-PRKACA chimeric fusion transcript. The paper outlines the advances made in understanding the molecular pathways driven by the fusion protein and the potential to identify actionable …

DNAJB1-PRKACA fusion protein-regulated LINC00473 promotes tumor growth and alters mitochondrial fitness in fibrolamellar carcinoma

While the role of the DNAJB1-PRKACA (DP) fusion protein in fibrolamellar carcinoma (FLC) was discovered a decade ago, it has been difficult to directly inhibit the function of this fusion protein. In this study, the investigators set out to identify downstream targets of the oncogene that could be exploited for new therapies. The investigators report …