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- Title
Targeting DNA Damage Repair Mechanisms in Pancreas Cancer.
- Authors
Perkhofer, Lukas; Golan, Talia; Cuyle, Pieter-Jan; Matysiak-Budnik, Tamara; Van Laethem, Jean-Luc; Macarulla, Teresa; Cauchin, Estelle; Kleger, Alexander; Beutel, Alica K.; Gout, Johann; Stenzinger, Albrecht; Van Cutsem, Eric; Bellmunt, Joaquim; Hammel, Pascal; O'Reilly, Eileen M.; Seufferlein, Thomas
- Abstract
Simple Summary: 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.
- Subjects
PANCREATIC tumors; ADENOCARCINOMA; PLATINUM compounds; CONSENSUS (Social sciences); GENETICS; GENETIC mutation; BRCA genes; ANTINEOPLASTIC agents; GENETIC testing; MEDICAL personnel; DUCTAL carcinoma; METABOLIC disorders; HEALTH literacy; SURVEYS; GENETIC engineering; EXPERTISE; DNA damage; DNA repair; ENZYME inhibitors
- Publication
Cancers, 2021, Vol 13, Issue 17, p4259
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers13174259