Classical elements.

Ancient Greek philosopher Empedocles first classified the material world into four elements: earth, water, air, and fire (yes it was Empedocles, not Captain Planet). Only 2.5 millennia later, we classify pancreatic cancer into four key driver mutations: KRAS, CDKN2A, SMAD4, and TP53. These were initially identified as “key” via whole exome sequencing and were later established as contributors to worse prognosis via rapid autopsy analyses. Last week’s JAMA Onc report confirms their prospective prognostic capabilities among 356 patients with resected pancreatic cancers at Dana Farber, Stanford, and the University of Rochester. Sure, this scratches some academic itches, but will it change practice? The answer is a hard maybe. We’re not there yet, but someday soon we may have the ability to tailor more aggressive therapies to those who are most likely to benefit, all based off genotyping of only four key mutations. Empedocles would be proud.