Fighting rare cancers: lessons from fibrolamellar hepatocellular carcinoma

Abstract

The fight against rare cancers faces myriad challenges, including missed or wrong diagnoses, lack of information and diagnostic tools, too few samples and too little funding. Yet many advances in cancer biology, such as the realization that there are tumour suppressor genes, have come from studying well-defined, albeit rare, cancers. Fibrolamellar hepatocellular carcinoma (FLC), a typically lethal liver cancer, mainly affects adolescents and young adults. FLC is both rare, 1 in 5 million, and problematic to diagnose. From the paucity of data, it was not known whether FLC was one cancer or a collection with similar phenotypes, or whether it was genetically inherited or the result of a somatic mutation. A personal journey through a decade of work reveals answers to these questions and a road map of steps and missteps in our fight against a rare cancer.

Development of pre-clinical murine models for fibrolamellar hepatocellular carcinoma

“…At the genetic level, a breakthrough in the field was the discovery of a fusion event resulting in high levels of the catalytic subunit of PKA (protein kinase A) in FLC tumors [20, 21]. This finding was confirmed in other studies [22-24].…”

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

“…Fibrolamellar carcinoma (FLC) is a liver tumor with no effective systemic treatments. 1 , 2 , 3 It occurs at an annual rate of 0.02 per 100,000 in the US 4 , 5 and predominantly affects adolescents and young adults without underlying liver pathology. 6 , 7 , 8 Surgical resection is typically the first line of treatment for FLC and can be curative for early-stage disease.…”

CDK7 is a Novel Therapeutic Vulnerability in Fibrolamellar Carcinoma

“…Fibrolamellar carcinoma (FLC) is a rare and lethal cancer that afflicts young individuals, and accounts for approximately 1% of liver cancers. [1][2][3][4] The tumor arises in the background of a normal liver, and patients typically present with advanced cancer at the time of diagnosis. 2,5 This is consequent to the absence of known risk factors or tumor markers that can precipitate screening or prevention.…”