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The 1988 paper that found a mutation in the KRAS gene in 21 of 22 pancreatic cancers, establishing the single most common driver in the disease and the target it took 33 more years to hit.
Almoguera, Shibata, Forrester, Martin, Arnheim and Perucho used polymerase chain reaction amplification and RNAase A mismatch cleavage to examine c-K-ras in human pancreatic carcinomas, in frozen specimens and single 5 micron sections of formalin-fixed tissue from surgery or autopsy. Twenty-one of 22 carcinomas of the exocrine pancreas carried c-K-ras mutations at codon 12; in seven cases tested the mutation was present in both the primary tumour and its metastases; no mutations were found in normal tissue from the same patients or in five gallbladder carcinomas. The authors concluded that somatic activation of c-K-ras is a critical event in the oncogenesis of most, if not all, cancers of the exocrine pancreas.
The reason pancreatic cancer is the proving ground for RAS drugs: nearly every tumour depends on the same mutant protein, so a drug that works against it works for nearly every patient.
Shares KRAS roadmap: undruggable → G12C → pan-RAS, The undruggable drivers, RAS / RAF / MEK / ERK (MAPK), 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 KRAS roadmap: undruggable → G12C → pan-RAS, KRAS mutation subtypes (G12C, G12D, G12V), RAS / RAF / MEK / ERK (MAPK), 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 RAS / RAF / MEK / ERK (MAPK), 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.
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.
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.