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, …

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 …

DNAJB1-PRKACA fusion drives fibrolamellar liver cancer through impaired SIK signaling and CRTC2/p300-mediated transcriptional reprogramming

Decoding the Cancer Mechanisms of Fibrolamellar Carcinoma: How DNAJB1-PRKACA drives Cancer Growth Critical cellular functions such as growth, survival, and communication with other cell types in the body are mediated by networks of proteins. These networks are normally tightly regulated by signaling molecules, which serve as on/off switches. Genetic changes can cause these signaling molecules …

NCI intramural program approach to rare tumors: Natural history study of rare solid tumors in children and adults: A longitudinal, comprehensive data and biospecimen collection protocol

Rare tumors contribute significantly to the burden of cancer in the United States, yet are often poorly understood and have inadequate research support. To address this situation, the National Cancer Institute’s (NCI) My Pediatric and Adult Rare Tumor Network (MyPART) was developed. MyPART’s goals include connecting participants and investigators through shared infrastructure and networks; accelerating …

MicroRNA-375 Suppresses the Growth and Invasion of Fibrolamellar Carcinoma

While the significance of the DNAJB1-PRKACA fusion gene in fibrolamellar carcinoma has been established and validated, the role of microRNAs (miRNAs) in FLC remains unclear. MicroRNAs have been implicated as drivers in many diseases including a variety of cancers. This study analyzed small RNA sequencing data to identify dysregulated miRNAs in FLC tumors and identified …

Reversing immunosuppression in the tumor microenvironment of fibrolamellar carcinoma via PD‑1 and IL‑10 blockade

Due to limited knowledge about the immune response to FLC, developing effective immunotherapy is challenging for the disease. In this study, the team investigated the immune environment of fibrolamellar carcinoma (FLC) using several techniques including multiplex immunohistochemistry and flow cytometry. Key findings of the effort include: Implications: The key takeaway of this study is that …

Detection of a recurrent DNAJB1-PRKACA chimeric transcript in fibrolamellar hepatocellular carcinoma

This study was the first published research effort that identified the DNAJB1-PRKACA chimeric transcript in fibrolamellar carcinoma tumors. By performing RNA sequencing on tumor and healthy tissue samples, a chimeric transcript was discovered that had not been previously reported in the literature. This fusion transcript arises due to a ~400-kilobase deletion on chromosome 19. In …

CRISPR/Cas9 Engineering of Adult Mouse Liver Demonstrates that the DNAJB1-PRKACA Gene Fusion Is Sufficient to Induce Tumors Resembling Fibrolamellar Hepatocellular Carcinoma

The DNAJB1-PRKACA fusion gene is found in almost all FLC tumors. In order to determine if this gene fusion is a cause of the tumors, these researchers used a CRISPR-Cas9 technique to create a chimeric DNAJB1-PRKACA fusion gene in the livers of otherwise healthy mice. Using the CRISPR-Cas9 system, the researchers created guide RNAs that …