# Rapid Drug Sensitivity Profiling via a Novel High-Success-Rate Culture Method for Patient-Derived Pancreatic Cancer: An Exploratory Preclinical Platform for Advancing Clinical Applications and Drug Development

**Authors:** Yu Kato, Naoki Yamamoto, Yuichiro Uchida, Noriko Hiramatsu, Takato Ozeki, Yukari Minobe, Yukika Hasegawa, Sho Kawabe, Hikaru Yabuuchi, Seiji Yamada, Yuko Hata, Eiji Sugihara, Tetsuya Takimoto, Kuniaki Saito, Takeshi Takahara, Koichi Suda, Osamu Nagano, Hideyuki Saya

PMC · DOI: 10.3390/cells15040313 · 2026-02-07

## TL;DR

A new high-success-rate culture method for pancreatic cancer cells enables drug sensitivity profiling and personalized treatment strategies.

## Contribution

A cost-effective, hydrogel-free culture system with over 90% success rate for patient-derived pancreatic cancer cells is introduced.

## Key findings

- The culture system maintains oncogenic KRAS mutations and a six-gene malignancy signature.
- Drug sensitivity profiling shows interpatient heterogeneity and potential clinical associations.
- The platform supports biomarker validation and testing of novel therapeutics like antibody–drug conjugates.

## Abstract

What are the main findings?
A cost-effective, hydrogel-free adherent culture system for patient-derived pancreatic cancer cells was established with a high success rate exceeding 90%.The cultured cells maintain essential oncogenic KRAS mutations and exhibit a consistent six-gene malignancy signature, including fibroblast activation protein (FAP) and WNT5A.

A cost-effective, hydrogel-free adherent culture system for patient-derived pancreatic cancer cells was established with a high success rate exceeding 90%.

The cultured cells maintain essential oncogenic KRAS mutations and exhibit a consistent six-gene malignancy signature, including fibroblast activation protein (FAP) and WNT5A.

What are the implication of the main findings?
This platform enables rapid and accurate drug sensitivity profiling that shows potential associations with clinical trends, serving as a practical tool for functional precision medicine.The high-purity cancer cell population supports an exploratory preclinical platform and biomarker validation for novel therapeutics, such as antibody–drug conjugates and immune checkpoint inhibitors.

This platform enables rapid and accurate drug sensitivity profiling that shows potential associations with clinical trends, serving as a practical tool for functional precision medicine.

The high-purity cancer cell population supports an exploratory preclinical platform and biomarker validation for novel therapeutics, such as antibody–drug conjugates and immune checkpoint inhibitors.

Pancreatic cancer is a highly intractable malignancy that necessitates personalized treatment strategies. Conventional patient-derived models, such as three-dimensional organoids, are often limited by intellectual property constraints and high costs. In this study, we developed an affordable adherent culture system for patient-derived pancreatic cancer cells using a proprietary medium and laminin-coated dishes. Primary cultures were successfully established from 28 patients with pancreatic ductal adenocarcinoma, exceeding a 90% success rate. Validation of eight samples confirmed maintenance of epithelial cell adhesion molecule expression and preservation of oncogenic KRAS mutations. Transcriptomic profiling revealed consistent upregulation of a six-gene signature (FAP, IGFBP5, PRRX1, SPARC, WNT5A, and ADAMTS12), which is associated with malignancy. In vitro drug sensitivity assays revealed interpatient heterogeneity with preliminary clinical associations. In conclusion, this simplified platform provides high-purity cancer cells and serves as a functional precision medicine tool. Beyond conventional chemotherapy, this platform has the potential to support applications ranging from biomarker validation and exploratory preclinical testing of novel therapeutics, including immune checkpoint inhibitors and antibody–drug conjugates. This optimization can lead to personalized therapeutic strategies for pancreatic cancer.

## Linked entities

- **Genes:** KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845], FAP (fibroblast activation protein alpha) [NCBI Gene 2191], IGFBP5 (insulin like growth factor binding protein 5) [NCBI Gene 3488], PRRX1 (paired related homeobox 1) [NCBI Gene 5396], SPARC (secreted protein acidic and cysteine rich) [NCBI Gene 6678], WNT5A (Wnt family member 5A) [NCBI Gene 7474], ADAMTS12 (ADAM metallopeptidase with thrombospondin type 1 motif 12) [NCBI Gene 81792]
- **Diseases:** pancreatic cancer (MONDO:0005192), pancreatic ductal adenocarcinoma (MONDO:0005184)

## Full-text entities

- **Genes:** LCN2 (lipocalin 2) [NCBI Gene 3934] {aka 24p3, MSFI, NGAL, p25}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, SERPINA3 (serpin family A member 3) [NCBI Gene 12] {aka AACT, ACT, GIG24, GIG25}, DUOX2 (dual oxidase 2) [NCBI Gene 50506] {aka LNOX2, NOXEF2, P138-TOX, TDH6, THOX2}, PRRX1 (paired related homeobox 1) [NCBI Gene 5396] {aka AGOTC, PHOX1, PMX1, PRX-1, PRX1}, ADAMTS12 (ADAM metallopeptidase with thrombospondin type 1 motif 12) [NCBI Gene 81792] {aka PRO4389}, COL1A2 (collagen type I alpha 2 chain) [NCBI Gene 1278] {aka EDSARTH2, EDSCV, OI4}, SPARC (secreted protein acidic and cysteine rich) [NCBI Gene 6678] {aka BM-40, OI17, ON, ONT}, CPA2 (carboxypeptidase A2) [NCBI Gene 1358], FAP (fibroblast activation protein alpha) [NCBI Gene 2191] {aka DPPIV, FAPA, FAPalpha, SIMP}, ACTB (actin beta) [NCBI Gene 60] {aka BKRNS, BNS, BRWS1, CSMH, DDS1, PS1TP5BP1}, COL3A1 (collagen type III alpha 1 chain) [NCBI Gene 1281] {aka EDS4A, EDSVASC, PMGEDSV}, SULF1 (sulfatase 1) [NCBI Gene 23213] {aka SULF-1}, KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}, GKN1 (gastrokine 1) [NCBI Gene 56287] {aka AMP18, BRICD1, CA11, FOV, foveolin}, EPCAM (epithelial cell adhesion molecule) [NCBI Gene 4072] {aka Ber-Ep4, BerEp4, DIAR5, EGP-2, EGP314, EGP40}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, IGFBP5 (insulin like growth factor binding protein 5) [NCBI Gene 3488] {aka IBP5}, WNT5A (Wnt family member 5A) [NCBI Gene 7474] {aka hWNT5A}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, HSPB6 (heat shock protein family B (small) member 6) [NCBI Gene 126393] {aka HEL55, Hsp20, PPP1R91}
- **Diseases:** cancers (MESH:D009369), PK (MESH:C564858), inflammation (MESH:D007249), injury to (MESH:D014947), PDAC (MESH:D021441), Pancreatic Cancer (MESH:D010190), T (MESH:D001260), N (MESH:C536108)
- **Chemicals:** SN-38 (MESH:D000077146), EDTA (MESH:D004492), paclitaxel (MESH:D017239), Streptomycin (MESH:D013307), WST-8 (MESH:C476329), paraffin (MESH:D010232), CCK-8 (MESH:D012844), Alexa488 (-), Hematoxylin (MESH:D006416), Penicillin (MESH:D010406), PCT (MESH:D011080), gemcitabine (MESH:D000093542), eosin (MESH:D004801), 3,3'-diaminobenzidine (MESH:D015100), Poly(A) (MESH:D011061), DAPI (MESH:C007293), Formalin (MESH:D005557)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** G12V, G12R
- **Cell lines:** S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232), HM25-012 — Homo sapiens (Human), Laryngeal squamous cell carcinoma, Cancer cell line (CVCL_5987), PK-56N — Mus musculus (Mouse), Mouse neuroblastoma, Cancer cell line (CVCL_WI10), PK-56T — Mus musculus (Mouse), Factor-dependent cell line (CVCL_C4TM), HG23-008 — Homo sapiens (Human), Adult hepatocellular carcinoma, Cancer cell line (CVCL_RW46), CRL-1682 — Rattus norvegicus (Rat), Rat hepatocellular carcinoma, Cancer cell line (CVCL_F665), AsPC-1 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_0152)

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12939418/full.md

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Source: https://tomesphere.com/paper/PMC12939418