Applications and challenges of patient-derived organoids in hepatobiliary and pancreatic cancers

Table 1 Types of established patient-derived hepatobiliary and pancreatic cancer organoids

Tumor type	Sample source	Success rate (sample size)	Drug testing	Time	Quality grade	Ref.
HCC, cholangiocarcinoma, combined hepatocellular cholangiocarcinoma	Res	25.0% (3/12), 75.0% (3/4), 100.0% (2/2)	29 anti-cancer compounds	2017	Low	Broutier et al[31]
HCC, ICC	Bx	33.0% (8/24), 60.0% (3/5)	Sorafenib	2018	Low	Nuciforo et al[30]
HCC, ICC	Res	40.9% (27/66)	Common clinical regimens	2024	Medium	Rao et al[22]
HCC, ICC	Res	75.6% (399/528)	Common clinical regimens	2024	High	Yang et al[11]
HCC, ICC	Res	> 60% (64/N/A)	301 compounds	2024	High	Walz et al[47]
HCC	Res or Bx	54.5% (12/22)	Common clinical regimens	2023	Medium	Zou et al[32]
ICC, GBC, PDAC	Res	50% (3/6), 20% (1/5), 50% (1/2)	339 anti-cancer compounds	2019	Low	Saito et al[35]
GBC	Res	12.2% (5/41)	29 anti-cancer compounds	2022	Low	Yuan et al[36]
ICC	Res or Bx	69.5% (16/23)	Gemcitabine and cisplatin	2023	Medium	Lee et al[33]
ECC, GBC, ICC	Res, Res, Res or Bx	81.3% (13/16), 40.0% (4/10), 82.6% (38/46)	Common clinical regimens	2023	Medium	Ren et al[34]
GBC, ECC	Res	85.7% (6/7)	Common clinical regimens	2021	Low	Wang et al[25]
PDAC	Res	80.0% (8/10)	N/A	2015	Low	Boj et al[37]
PDAC	Res or Bx	73% (101/138)	Fluorouracil	2018	High	Tiriac et al[38]
PC, ECC	Res or Bx	62.6% (52/83)	Common clinical regimens	2019	High	Driehuis et al[43]
IPMN	Res	81.3% (13/16)	N/A	2021	Medium	Beato et al[39]
PDAC	Res or Bx	37%-60% (36/N/A)	Common clinical regimens	2024	Medium	Kim et al[40]
PC	Bx	48.1% (13/27)	Common clinical regimens	2023	Medium	Choi et al[42]
PC	Bx	93.3% (14/15)	Common clinical regimens	2024	Medium	Yang et al[14]
Cholangiocarcinoma, GBC, perihilar cholangiocarcinoma, PDAC, IPMN	Res	60.0% (12/20), 100.0% (6/6), 100.0% (2/2), 40.0% (8/20), 33.3% (2/6)	Integrin-linked kinase inhibitor	2021	Medium	Shiihara et al[41]

Studies with fewer than 10 successful cultures are classified as having low prevalence, those with 10–50 successful cultures are considered to have moderate prevalence, and studies with more than 50 successful cultures are considered to have high prevalence. Bx: Biopsy; ECC: Extrahepatic cholangiocarcinoma; GBC: Gallbladder cancer; HCC: Hepatocellular carcinoma; ICC: Intrahepatic cholangiocarcinoma; IPMN: Intraductal papillary mucinous neoplasm; N/A: Not available; PC: Pancreatic cancer; PDAC: Pancreatic ductal adenocarcinoma; Res: Resection.

Table 2 Co-culture model of patient-derived organoids for hepatobiliary and pancreatic cancer

Tumor cells	Co-culture cells	Ratio (co-culture cells: Tumor cells)	Culture time (day)	Pattern	Ref.
HCC	T cells	10:1	1	Direct 3D co-culture	Liu et al[62]
HCC, intrahepatic cholangiocarcinoma	CAFs	2:1	10-14	Transwell culture	Liu et al[51]
HCC	PBMC, MSC	30:1:10	7	Chip	Zou et al[32]
HCC	T cells	10:1	1	Direct 3D co-culture	Zou et al[63]
Cholangiocarcinoma	T cells	25–50:1	7	Direct 3D co-culture	Zhou et al[64]
Extrahepatic cholangiocarcinoma	TAMs	1:5	14	Transwell culture	Guo et al[27]
PDAC	MSC, T cells	N/A	5	Direct 3D co-culture	Tai et al[65]
PDAC	CAFs	2:1	5	Transwell culture	Tao et al[60]
PDAC	TAMs	1:1	6	ALI culture	Tabe et al[58]
PDAC	MSC, endothelial cells	60:21:30	7	ALI culture	Takeuchi et al[61]
PDAC	CAFs	1:1	10	Transwell culture	Sheng et al[66]
PDAC	T cells	10:1	3	Hydrogel chip	Lahusen et al[67]
PC	TAMs	3:1	N/A	Transwell culture	Jiang et al[59]
PDAC	NK cells	2-5:1	3	Transwell culture	Beelen et al[68]
PC	CAFs	1:1	3	Transwell culture	Schuth et al[69]
PDAC	CAFs	20:1	10	Transwell culture	Shinkawa et al[70]
PDAC	T cells	1:1	14	Direct 3D co-culture	Meng et al[71]
PDAC	PBMC, NK cells	N/A	7–14	Direct 3D co-culture	Marcon et al[72]
PDAC	CAFs, T cells	N/A	3	Direct 3D co-culture	Tsai et al[73]

ALI: Air-liquid interface; CAFs: Cancer-associated fibroblasts; HCC: Hepatocellular carcinoma; MSC: Mesenchymal stem cells; N/A: Not available; NK: Natural killer; PBMC: Peripheral blood mononuclear cells; PC: Pancreatic cancer; PDAC: Pancreatic ductal adenocarcinoma; TAMs: Tumor-associated macrophages; 3D: Three-dimensional.