ALK and neuroblastoma: Additionally, neuroblastoma cells driven by MYCN and ALK amplifications can acquire resistance via a multi-step process in which they downregulate MYCN, and instead upregulate and become dependent on BORIS, a DNA binding protein that increases the proliferation and survival of cancer cells, and here causes increased expression of transcription factors that promote the transformation to an ALK TKI-resistant phenotype [156,157].