Tyrosine kinase, when mutated, causes uncontrolled cell growth.<p>TKIs: Crizotinib (1st gen), alectinib.<p>>> Lorlatinib is a third-generation, highly potent, macrocyclic ALK/ROS1 TKI that competitively binds to the adenosine triphosphate‐binding pocket, blocking ALK‐dependent oncogenic signaling. The advantage of Lorlatinib is high penetration of the blood-brain barrier by decreasing p‐glycoprotein‐1‐mediated efflux. Besides, it has broad‐spectrum activity against most known resistance mutations that develop during treatment with first and second‐generation ALK TKIs, including ALK G1202R mutation. The introduction of Lorlatinib to salvage these patients has shown the potential to add life. This has been shown in a global phase II study and other real-world studies, however, data is scant from LMIC. The most common toxicities were peripheral edema (9–48%), hyperlipidemia (47–94%), weight gain (3–25%), peripheral neuropathy (30%), fatigue (15–30%) and cognitive effect (6–18%) in earlier studies. The treatment discontinuation rate varied from 3–14% due to toxicity.<p><a href="https://www.nature.com/articles/s44276-024-00055-9" rel="nofollow">https://www.nature.com/articles/s44276-024-00055-9</a><p><a href="https://en.wikipedia.org/wiki/Lorlatinib" rel="nofollow">https://en.wikipedia.org/wiki/Lorlatinib</a><p><a href="https://en.wikipedia.org/wiki/Tyrosine_kinase" rel="nofollow">https://en.wikipedia.org/wiki/Tyrosine_kinase</a>