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Histological and molecular plasticity of ALK-positive non-small-cell lung cancer under targeted therapy: a case report

Beitrag vom 20. Juli 2022

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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 nonsmall-cell lung cancer treated with four different TKIs. Her tumor developed not only a wellknown 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.

Histological and molecular plasticity of ALK-positive non-small-cell lung cancer under targeted therapy: a case report Histological and molecular plasticity of ALK-positive non-small-cell lung cancer under targeted therapy: a case report

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