With medical progress in cancer therapy, tyrosine kinase inhibitors (TKIs) became a standard of care for many cancer types. But the broad range of possible targeted therapies was accompanied by a plethora of potential resistance mechanisms, of which many have still to be identified. Here, we present the case of a patient with an EML4-ALK translocated non-small-cell lung cancer treated with four different TKIs. His tumor developed not only a well-known ALK-TKI resistance mutation, but also underwent a histological transformation from adenocarcinoma to squamous cell carcinoma. To confirm a shared monoclonal origin of the phenotypically different tumors, a phylogenetic reconstruction was conducted: this revealed a cluster of mutations including NFE2L2, KMT2D and MLH1 which are possible triggering events for the transformation. READ ARTICLE
Cold Spring Harbor Molecular Case Studies DOI:10.1101/mcs.a006156
Authors: Markus Ball, Petros Christopoulos, Martina Kirchner, Michael Allgaeuer, Regine Brandt, Hauke Winter, Claus Peter Heussel, Felix Herth, Stefan Froehling, Rajkumar Savai, Mark Kriegsmann, Peter Schirmacher, Solange Peters, Michael Thomas, Albrecht Stenzinger, Daniel Kazdal