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.
- Ball, M.
- Christopoulos, P.
- Kirchner, M.
- Allgaeuer, M.
- Brandt, R.
- Winter, H.
- Heussel, C. P.
- Herth, F.
- Froehling, S.
- Savai, R.
- Kriegsmann, M.
- Schirmacher, P.
- Peters, S.
- Thomas, M.
- Stenzinger, A.
- Kazdal, D.
