NDLI: Increased HRD score in cisplatin resistant penile cancer cells

Content Provider	Springer Nature : BioMed Central
Author	Winkelmann, Ria Bankov, Katrin Döring, Claudia Cinatl, Jaroslav Grothe, Sebastian Rothweiler, Florian Michaelis, Martin Schmitt, Christina Wild, Peter J. Demes, Melanie Cinatl, Jindrich Vallo, Stefan
Abstract	Background/Introduction 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. Methods 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-1rCDDP2500, adapted to 2500 ng/ml CDDP; UKF-PEC-1r5-FU500, adapted to 500 ng/ml 5- FU; UKF-PEC1rCDDP2500/r5-FU500, 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-1rCDDP2500, UKF-PEC-1r5-FU500, UKF-PEC1rCDDP2500/r5-FU500, and UKF-PEC-3 (an alternative penis cancer cell line) were tested for sensitivity to paclitaxel, docetaxel, olaparib, and rucaparib. Results and conclusions The chemo-resistant sublines differed in their mutational landscapes. UKF-PEC-1rCDDP2500 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-1rCDDP2500 did not display sensitivity to PARP inhibitors.
Related Links	https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-022-10432-7.pdf
Ending Page	14
Page Count	14
Starting Page	1
File Format	HTM / HTML
ISSN	14712407
DOI	10.1186/s12885-022-10432-7
Journal	BMC Cancer
Issue Number	1
Volume Number	22
Language	English
Publisher	BioMed Central
Publisher Date	2022-12-23
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Surgical Oncology Health Promotion and Disease Prevention Biomedicine Medicine Public Health Penile carcinomas Cell lines Chemoresistance Homologous recombination deficiency Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology Genetics
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.8/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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