2024 Archives - Fibrolamellar Cancer Foundation

Proteo-metabolomics and patient tumor slice experiments point to amino acid centrality for rewired mitochondria in fibrolamellar carcinoma

Proteomics studies assess the composition, structure, expression, and the interactions and connections between proteins at an overall level in tissue. Metabolomics studies focus on characterizing metabolites, the small molecules generated by specific cellular processes. Both types of studies can yield valuable insights into the complex biochemical pathways, networks, and molecular systems that control important cell …

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 …

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 …

Serum Procalcitonin: A Novel Tumor Biomarker for Diagnosis and Follow-Up in Fibrolamellar Hepatocellular Carcinoma

Doctors have long struggled to diagnose and monitor FLC partially because no blood tests (biomarkers) work reliably for it. Standard liver cancer markers like alpha-fetoprotein (AFP) are almost always normal in FLC. This study reports a new and promising discovery: procalcitonin (PCT), a blood marker normally used to detect bacterial infections, turns out to be …

DNAJB1-PRKACA fusion neoantigens elicit rare endogenous T cell responses that potentiate cell therapy for fibrolamellar carcinoma

In this study, published in March 2024, the researchers looked at how a patient’s immune system responds to the protein produced by the fusion of the genes DNAJB1 and PRKACA in FLC. Specifically, the team aimed to understand how the immune system’s “killer” T cells (CD8s) respond to this mutation and evaluate T cell receptors …

Liver cancer multiomics reveals diverse protein kinase A disruptions convergently produce fibrolamellar hepatocellular carcinoma

This study represents one of the most comprehensive molecular analyses performed on fibrolamellar carcinoma (FLC). Using more than 1,400 tumor and normal liver samples, including 220 FLC and FLC‑like tumors, the research team used techniques including RNA sequencing, DNA sequencing, proteomics, methylation analysis, and spatial single‑cell mapping to better understand FLC at the molecular level. …

Rare primary liver cancers: An EASL position paper

The European Association for the Study of the Liver (EASL) convened an international, multidisciplinary panel to evaluate and summarize current knowledge on rare primary liver cancers. The resulting paper focused in three major rare liver cancers, combined hepatocellular–cholangiocarcinoma (cHCC‑CCA), fibrolamellar carcinoma (FLC), and hepatic epithelioid hemangioendothelioma (HEHE), as well as several ultra‑rare varieties. Due to …