ALK+ Cancer

ALK+ cancer refers to malignancies characterized by aberrant activation of the anaplastic lymphoma kinase (ALK) gene, typically through chromosomal translocations that create fusion proteins with constitutive kinase activity.

ALK is a receptor tyrosine kinase normally expressed at low levels in specific neural tissues during development. In ALK+ cancers, fusion events—most commonly involving the NPM1 gene in lymphomas or EML4 in lung adenocarcinomas—produce chimeric proteins that drive uncontrolled cell proliferation and survival. These fusion events occur in approximately 3-5% of non-small cell lung cancers and are also found in anaplastic large cell lymphomas, inflammatory myofibroblastic tumors, and other malignancies.

The discovery of ALK fusions revolutionized cancer treatment, as these tumors are highly sensitive to ALK-targeted tyrosine kinase inhibitors (TKIs). Crizotinib was the first approved ALK inhibitor, followed by more potent second- and third-generation agents like alectinib, ceritinib, and brigatinib. These targeted therapies have dramatically improved outcomes compared to conventional chemotherapy, though resistance through secondary ALK mutations and bypass pathway activation remains a clinical challenge.

ALK status is now routinely tested in lung adenocarcinomas and certain lymphomas to guide treatment decisions. The presence of ALK fusion is generally associated with younger patient age, adenocarcinoma histology, and non-smoking status in lung cancer populations.

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