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The 2015 whole-genome study of 100 pancreatic cancers that sorted them by how broken their chromosomes were and noticed that the most unstable tumours, often with BRCA-type defects, responded to platinum chemotherapy.
Waddell and colleagues of the Australian Pancreatic Cancer Genome Initiative performed whole-genome sequencing and copy number analysis of 100 pancreatic ductal adenocarcinomas. Chromosomal rearrangements disrupting known genes (TP53, SMAD4, CDKN2A, ARID1A, ROBO2) and new candidates (KDM6A, PREX2) were prevalent. Patterns of structural variation classified the tumours into four subtypes: stable, locally rearranged, scattered and unstable. Focal amplifications containing druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3, PIK3CA) were found at low individual prevalence. Genomic instability co-segregated with inactivation of BRCA1, BRCA2 or PALB2 and a DNA damage repair deficiency signature; of eight patients who received platinum, four of five with these measures of defective DNA maintenance responded.
The genomic case for platinum in BRCA-type pancreatic cancer, four years before POLO built a maintenance strategy on top of it.
Shares POLO: maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer, Germline BRCA mutation (gBRCA), BRCA or PALB2-mutant pancreatic ductal adenocarcinoma, BRCA1 / BRCA2 (HRD) and the tag pancreatic-evidence.
Shares Germline BRCA mutation (gBRCA), BRCA or PALB2-mutant pancreatic ductal adenocarcinoma, BRCA1 / BRCA2 (HRD), Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question and the tag pancreatic-evidence.
Shares POLO: maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer, Germline BRCA mutation (gBRCA), Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Genomic analyses identify molecular subtypes of pancreatic cancer, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Nature, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Nature, Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.
Shares Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question, Pancreatic ductal adenocarcinoma and the tag pancreatic-evidence.