Table 1 |.

Currently available models for fibrolamellar carcinoma research

Model	Type	Species	Method	Strengths	Limitations	Refs
Published work
M-DP-1	In vivo	Mouse	CRISPR–Cas9-based genome editing Transposon-mediated somatic gene transfer	In vivo tumour growth Mimics many features of FLC	Slow tumorigenesis Incomplete penetrance Lacks fibrous bands Lacks molecular features of FLC that are primate-specific	58
M-DP-2	In vivo	Mouse	CRISPR–Cas9-based genome editing	In vivo tumour growth Mimics many features of FLC	Slow tumorigenesis Incomplete penetrance Lacks fibrous bands Lacks molecular features of FLC that are primate-specific	57
ZF-DP-1	In vivo	Zebrafish	Zebrafish DNAJ–PKAc over-expression	In vivo model	Evolutionarily more distant from humans than mice Lacks molecular features specific to mammals and primates	96
PDX-1	In vivo	Human	Xenograft of patient-derived FLC tumour cells in immune-deficient mice	In vivo tumour growth Mimics most/all major features of FLC Can be maintained stably in spheroid (3D) culture	Generally, tumour grown in host flank, not liver (non-orthotopic model) Not metastatic from flank	36
PDX-2 to PDX-7	In vivo	Human	Xenograft of patient-derived FLC tumour cells in immune-deficient mice	In vivo tumour growth Mimics most/all major features of FLC Derived directly from primary Liver tumours and metastases	Generally, tumour grown in host flank, not liver (non-orthotopic model) Not metastatic from flank	97
HepG2-DP	In vitro	Human	Lentiviral DP over-expression	All human cells Straightforward to culture and manipulate	No presence of cells from microenvironment Hepatoblastoma background Transformed cells	33,50
C3A-DP	In vitro	Human	LentiviraL DP over-expression	All human cells Straightforward to culture and manipulate	No presence of cells from microenvironment HCC background Transformed cells	33
AML12-DP	In vitro	Mouse	CRISPR–Cas9-based genome editing	Primary hepatocytes Straightforward to culture and manipulate	Mouse not human origin Transgenic for human TGFα	50,76,89
Unpublished or preliminary work
FLX-1 cell line	In vitro	Human	Cell culture from PDX-1 xenograft model	(Nearly) all human tumour cells Established line that retains molecular features of FLC for multiple passages Amenable to treatment and transfection	Limited (if any) microenvironmental signalling Relatively slow growth	N. Bardeesy (personal communication)
Huh7-DP	In vitro	Human	Lentiviral DP over-expression	All human cells Straightforward to culture and manipulate	No presence of cells from microenvironment HCC background Transformed cells	P.S., unpublished work
HEK293-DP	In vitro	Human	CRISPR– Cas9-based genome editing	All human cells Straightforward to culture and manipulate	No presence of cells from microenvironment Non-hepatic background Transformed cells	95 (a preprint article)

All of these 16 in vitro and in vivo models currently in use for fibrolamellar carcinoma (FLC) research offer some strengths but also have key limitations, pointing to the critical need for improved models. DP, DNAJB1–PRKACA; HCC, hepatocellular carcinoma; TGFα, transforming growth factor-α.