Anaplastic lymphoma receptor tyrosine kinase (ALK) (ALK)

Anaplastic lymphoma receptor tyrosine kinase (ALK) is a member of the insulin receptor superfamily that plays a vital role in the development and function of the nervous system [1]. While its physiological expression is largely restricted to the embryonic and neonatal brain, ALK is a well-known proto-oncogene that can be activated in various cancers through gene fusions, point mutations, or amplification [4]. The most common oncogenic driver is the EML4-ALK fusion, which occurs in a subset of non-small cell lung cancers (NSCLC) and results in constitutive kinase activity [3]. This aberrant signaling activates multiple pathways, including PI3K/AKT and MAPK/ERK, which promote cell survival and proliferation [1]. Therapeutic strategies utilize ALK inhibitors, such as alectinib, which target the ATP-binding pocket of the kinase domain [2]. Alectinib is unique because it is metabolized into a major active metabolite, M4 (N-deethylalectinib), which maintains similar potency against ALK and contributes to the drug's overall clinical efficacy and its ability to cross the blood-brain barrier [2, 3].

Other names

ALKCD246Anaplastic lymphoma kinaseALK tyrosine kinase receptorAnaplastic lymphoma receptor tyrosine kinase

Inhibition of the tyrosine kinase activity of the ALK protein by competing with ATP for the binding site, thereby blocking downstream signaling pathways such as STAT3, PI3K/AKT, and MAPK/ERK that drive tumor cell proliferation and survival [1, 2].