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Conference Report

Targeting DNA Damage Repair Mechanisms in Pancreas Cancer

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Department of Internal Medicine I, Ulm University Hospital, 89081 Ulm, Germany
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Oncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv 52621, Israel
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Digestive Oncology Department, Imelda General Hospital, 2820 Bonheiden, Belgium
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University Hospitals Gasthuisberg Leuven and KU Leuven, 3000 Leuven, Belgium
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IMAD, Department of Gastroenterology and Digestive Oncology, Hôtel Dieu, CHU de Nantes, 44000 Nantes, France
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GI Cancer Unit, Erasme Hospital, Université Libre de Bruxelles, 1070 Brussels, Belgium
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Vall d’Hebrón University Hospital and Vall d’Hebron Institute of Oncology, 08035 Barcelona, Spain
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Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany
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Medical Oncology, University Hospital del Mar, 08003 Barcelona, Spain
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Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
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Hôpital Beaujon, 92110 Clichy, France
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Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
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Department of Medicine, David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Yasushi Sato
Cancers 2021, 13(17), 4259; https://doi.org/10.3390/cancers13174259
Received: 27 July 2021 / Accepted: 6 August 2021 / Published: 24 August 2021
Pancreatic cancer is a devastating malignant disease with a dismal prognosis and limited treatment options. Around 14% of pancreatic cancers harbour mutations in specific genes that are important to ensure appropriate DNA repair after damage, like the BRCA 1 and 2 genes. Recently, with olaparib a first treatment option for BRCA 1 and 2 mutated pancreatic cancer was approved. However, there is a relevant proportion of further genes involved in the DNA damage repair beyond BRCA1 and 2 that might benefit from such tailored therapeutic interventions like olaparib. Unfortunately, due to the lack of specific data, no general recommendations are currently available. Therefore, a representative panel of experts was assembled by the European Society of Digestive Oncology (ESDO) to assess the current knowledge and evaluate the significance to treat pancreatic cancer with mutations in DNA damage repair genes. The data-driven consensus recommendations of the ESDO expert panel aim to provide clinicians guidance for a state-of-the-art management.
Impaired DNA damage repair (DDR) is increasingly recognised as a hallmark in pancreatic ductal adenocarcinoma (PDAC). It is estimated that around 14% of human PDACs harbour mutations in genes involved in DDR, including, amongst others, BRCA1/2, PALB2, ATM, MSH2, MSH6 and MLH1. Recently, DDR intervention by PARP inhibitor therapy has demonstrated effectiveness in germline BRCA1/2-mutated PDAC. Extending this outcome to the significant proportion of human PDACs with somatic or germline mutations in DDR genes beyond BRCA1/2 might be beneficial, but there is a lack of data, and consequently, no clear recommendations are provided in the field. Therefore, an expert panel was invited by the European Society of Digestive Oncology (ESDO) to assess the current knowledge and significance of DDR as a target in PDAC treatment. The aim of this virtual, international expert meeting was to elaborate a set of consensus recommendations on testing, diagnosis and treatment of PDAC patients with alterations in DDR pathways. Ahead of the meeting, experts completed a 27-question survey evaluating the key issues. The final recommendations herein should aid in facilitating clinical practice decisions on the management of DDR-deficient PDAC. View Full-Text
Keywords: DNA damage repair; pancreatic ductal adenocarcinoma; BRCA1/2; PARP inhibition; platinum; homologous repair deficiency DNA damage repair; pancreatic ductal adenocarcinoma; BRCA1/2; PARP inhibition; platinum; homologous repair deficiency
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MDPI and ACS Style

Perkhofer, L.; Golan, T.; Cuyle, P.-J.; Matysiak-Budnik, T.; Van Laethem, J.-L.; Macarulla, T.; Cauchin, E.; Kleger, A.; Beutel, A.K.; Gout, J.; Stenzinger, A.; Van Cutsem, E.; Bellmunt, J.; Hammel, P.; O’Reilly, E.M.; Seufferlein, T. Targeting DNA Damage Repair Mechanisms in Pancreas Cancer. Cancers 2021, 13, 4259. https://doi.org/10.3390/cancers13174259

AMA Style

Perkhofer L, Golan T, Cuyle P-J, Matysiak-Budnik T, Van Laethem J-L, Macarulla T, Cauchin E, Kleger A, Beutel AK, Gout J, Stenzinger A, Van Cutsem E, Bellmunt J, Hammel P, O’Reilly EM, Seufferlein T. Targeting DNA Damage Repair Mechanisms in Pancreas Cancer. Cancers. 2021; 13(17):4259. https://doi.org/10.3390/cancers13174259

Chicago/Turabian Style

Perkhofer, Lukas, Talia Golan, Pieter-Jan Cuyle, Tamara Matysiak-Budnik, Jean-Luc Van Laethem, Teresa Macarulla, Estelle Cauchin, Alexander Kleger, Alica K. Beutel, Johann Gout, Albrecht Stenzinger, Eric Van Cutsem, Joaquim Bellmunt, Pascal Hammel, Eileen M. O’Reilly, and Thomas Seufferlein. 2021. "Targeting DNA Damage Repair Mechanisms in Pancreas Cancer" Cancers 13, no. 17: 4259. https://doi.org/10.3390/cancers13174259

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