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Increased HRD score in cisplatin resistant penile cancer cells

Winkelmann, Ria, Bankov, Katrin, Döring, Claudia, Cinatl, Jaroslav, Grothe, Sebastian, Rothweiler, Florian, Michaelis, Martin, Schmitt, Christina, Wild, Peter J, Demes, Melanie, and others. (2022) Increased HRD score in cisplatin resistant penile cancer cells. BMC Cancer, 22 (1). Article Number 1352. ISSN 1471-2407. (doi:10.1186/s12885-022-10432-7) (KAR id:99423)


Penile cancer is a rare disease in demand for new therapeutic options. Frequently used combination chemotherapy with 5 fluorouracil (5-FU) and cisplatin (CDDP) in patients with metastatic penile cancer mostly results in the development of acquired drug resistance. Availability of cell culture models with acquired resistance against standard therapy could help to understand molecular mechanisms underlying chemotherapy resistance and to identify candidate treatments for an efficient second line therapy. We generated a cell line from a humanpapilloma virus (HPV) negative penile squamous cell carcinoma (UKF-PEC-1). This cell line was subject to chronic exposure to chemotherapy with CDDP and / or 5-FU to induce acquired resistance in the newly established chemo-resistant sublines (PEC-1 CDDP , adapted to 2500 ng/ml CDDP; UKF-PEC-1 5-FU , adapted to 500 ng/ml 5- FU; UKF-PEC1 CDDP / 5-FU , adapted to 2500 ng/ml CDDP and 500 ng/ml 5 -FU). Afterwards cell line pellets were formalin-fixed, paraffin embedded and subject to sequencing as well as testing for homologous recombination deficiency (HRD). Additionally, exemplary immunohistochemical stainings for p53 and gammaH2AX were applied for verification purposes. Finally, UKF-PEC-1 CDDP , UKF-PEC-1 5-FU , UKF-PEC1 CDDP / 5-FU , and UKF-PEC-3 (an alternative penis cancer cell line) were tested for sensitivity to paclitaxel, docetaxel, olaparib, and rucaparib. The chemo-resistant sublines differed in their mutational landscapes. UKF-PEC-1 CDDP was characterized by an increased HRD score, which is supposed to be associated with increased PARP inhibitor and immune checkpoint inhibitor sensitivity in cancer. However, UKF-PEC-1 CDDP did not display sensitivity to PARP inhibitors. [Abstract copyright: © 2022. The Author(s).]

Item Type: Article
DOI/Identification number: 10.1186/s12885-022-10432-7
Uncontrolled keywords: Drug Resistance, Neoplasm - genetics, Antineoplastic Combined Chemotherapy Protocols - pharmacology, Homologous recombination deficiency, Cisplatin - pharmacology - therapeutic use, Fluorouracil - pharmacology - therapeutic use, Humans, Cell Line, Tumor, Chemoresistance, Penile carcinomas, Penile Neoplasms - drug therapy, Cell lines, Male
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH581.2 Cell Biology
Divisions: Divisions > Division of Natural Sciences > Biosciences
SWORD Depositor: JISC Publications Router
Depositing User: JISC Publications Router
Date Deposited: 18 Jan 2023 15:16 UTC
Last Modified: 19 Jan 2023 12:30 UTC
Resource URI: (The current URI for this page, for reference purposes)

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