Genomic alterations involving the anaplastic lymphoma kinase (ALK) gene are known oncogenic drivers of a variety of malignancies [1-4]. In the wild-type state, activation of the ALK protein is thought to be potentially mediated by ligand-induced dimerization; however, the role that ALK plays in normal physiology remains poorly understood. Oncogenic activation of ALK can occur via a variety of mechanisms including mutation (e.g. in neuroblastomas) and recurrent gene rearrangements. In the rearranged state, the intact tyrosine kinase domain of ALK is fused to a variety of upstream partners, with the breakpoint of ALK being highly conserved across different fusions. These 5¿ partners contribute leucine zipper or coiled-coil domains that result in ligand-independent activation and constitutive activation of the ALK tyrosine kinase. This, in turn, results in activation of downstream signaling involving the MAPK, PI3K, and JAK/STAT pathways and increased cell growth and proliferation .
This phase II trial studies how well treatment that is directed by genetic testing works in patients with solid tumors or lymphomas that have progressed following at least one line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment which targets their tumor's particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors or lymphomas.