ALKpositive

ALKpositive describes tumors that harbor alterations in the anaplastic lymphoma kinase (ALK) gene, leading to abnormal ALK protein activity. The most common mechanism is chromosomal rearrangement creating fusion genes, such as EML4-ALK, which produce a constitutively active tyrosine kinase that drives oncogenic signaling and tumor growth.

ALK alterations occur in several cancers, most notably a subset of non-small cell lung cancer (NSCLC) and anaplastic large cell lymphoma (ALCL). In NSCLC, ALK rearrangements define a molecularly distinct subset that tends to occur in younger patients and those with little or no smoking history. ALK positivity is also described in other tumors, including inflammatory myofibroblastic tumors, neuroblastoma, and certain sarcomas, reflecting a broader role for ALK in oncogenesis.

Diagnosis typically begins with immunohistochemistry to detect ALK protein expression, followed by confirmatory testing with fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS) to demonstrate ALK rearrangement. The detection of ALK alterations has important therapeutic implications.

Treatment for ALK-positive cancers primarily involves targeted ALK inhibitors. In NSCLC, approved inhibitors such as crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib have demonstrated meaningful clinical benefit and durable responses in many patients, though resistance often develops and central nervous system progression can occur. In ALCL and other ALK-positive tumors, ALK inhibitors may be used in relapsed or refractory settings, with ongoing research to optimize sequencing and combination strategies.

Prognosis in ALK-positive disease varies by cancer type, stage, and response to targeted therapy, but ALK-directed treatment has substantially influenced outcomes for many patients.