Targeting DNA Damage Repair Mechanisms in Pancreas Cancer
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, <i>BRCA1/2</i>, <i>PALB2</i>, <i>A...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/17/4259 |
| _version_ | 1797521568455196672 |
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| author | Lukas Perkhofer 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 Thomas Seufferlein |
| author_facet | Lukas Perkhofer 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 Thomas Seufferlein |
| author_sort | Lukas Perkhofer |
| collection | DOAJ |
| description | 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, <i>BRCA1/2</i>, <i>PALB2</i>, <i>ATM</i>, <i>MSH2</i>, <i>MSH6</i> and <i>MLH1</i>. Recently, DDR intervention by PARP inhibitor therapy has demonstrated effectiveness in germline <i>BRCA1/2</i>-mutated PDAC. Extending this outcome to the significant proportion of human PDACs with somatic or germline mutations in DDR genes beyond <i>BRCA1/2</i> 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. |
| first_indexed | 2024-03-10T08:14:20Z |
| format | Article |
| id | doaj.art-22a0450c09e14674ac6c1e5c5e4597ea |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T08:14:20Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-22a0450c09e14674ac6c1e5c5e4597ea2023-11-22T10:24:35ZengMDPI AGCancers2072-66942021-08-011317425910.3390/cancers13174259Targeting DNA Damage Repair Mechanisms in Pancreas CancerLukas Perkhofer0Talia Golan1Pieter-Jan Cuyle2Tamara Matysiak-Budnik3Jean-Luc Van Laethem4Teresa Macarulla5Estelle Cauchin6Alexander Kleger7Alica K. Beutel8Johann Gout9Albrecht Stenzinger10Eric Van Cutsem11Joaquim Bellmunt12Pascal Hammel13Eileen M. O’Reilly14Thomas Seufferlein15Department of Internal Medicine I, Ulm University Hospital, 89081 Ulm, GermanyOncology Institute, Sheba Medical Center, Tel Aviv University, Tel Aviv 52621, IsraelDigestive Oncology Department, Imelda General Hospital, 2820 Bonheiden, BelgiumIMAD, Department of Gastroenterology and Digestive Oncology, Hôtel Dieu, CHU de Nantes, 44000 Nantes, FranceGI Cancer Unit, Erasme Hospital, Université Libre de Bruxelles, 1070 Brussels, BelgiumVall d’Hebrón University Hospital and Vall d’Hebron Institute of Oncology, 08035 Barcelona, SpainIMAD, Department of Gastroenterology and Digestive Oncology, Hôtel Dieu, CHU de Nantes, 44000 Nantes, FranceDepartment of Internal Medicine I, Ulm University Hospital, 89081 Ulm, GermanyDepartment of Internal Medicine I, Ulm University Hospital, 89081 Ulm, GermanyDepartment of Internal Medicine I, Ulm University Hospital, 89081 Ulm, GermanyInstitute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, GermanyUniversity Hospitals Gasthuisberg Leuven and KU Leuven, 3000 Leuven, BelgiumMedical Oncology, University Hospital del Mar, 08003 Barcelona, SpainHôpital Beaujon, 92110 Clichy, FranceGastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USADepartment of Internal Medicine I, Ulm University Hospital, 89081 Ulm, GermanyImpaired 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, <i>BRCA1/2</i>, <i>PALB2</i>, <i>ATM</i>, <i>MSH2</i>, <i>MSH6</i> and <i>MLH1</i>. Recently, DDR intervention by PARP inhibitor therapy has demonstrated effectiveness in germline <i>BRCA1/2</i>-mutated PDAC. Extending this outcome to the significant proportion of human PDACs with somatic or germline mutations in DDR genes beyond <i>BRCA1/2</i> 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.https://www.mdpi.com/2072-6694/13/17/4259DNA damage repairpancreatic ductal adenocarcinoma<i>BRCA1/2</i>PARP inhibitionplatinumhomologous repair deficiency |
| spellingShingle | Lukas Perkhofer 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 Thomas Seufferlein Targeting DNA Damage Repair Mechanisms in Pancreas Cancer Cancers DNA damage repair pancreatic ductal adenocarcinoma <i>BRCA1/2</i> PARP inhibition platinum homologous repair deficiency |
| title | Targeting DNA Damage Repair Mechanisms in Pancreas Cancer |
| title_full | Targeting DNA Damage Repair Mechanisms in Pancreas Cancer |
| title_fullStr | Targeting DNA Damage Repair Mechanisms in Pancreas Cancer |
| title_full_unstemmed | Targeting DNA Damage Repair Mechanisms in Pancreas Cancer |
| title_short | Targeting DNA Damage Repair Mechanisms in Pancreas Cancer |
| title_sort | targeting dna damage repair mechanisms in pancreas cancer |
| topic | DNA damage repair pancreatic ductal adenocarcinoma <i>BRCA1/2</i> PARP inhibition platinum homologous repair deficiency |
| url | https://www.mdpi.com/2072-6694/13/17/4259 |
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