STK11 alterations in the pan-cancer setting: prognostic and therapeutic  implications - ScienceDirect

STK11 mutation recently have become a biomarker and potential target of interest, especially for patients with lung cancer.

Recent trials explore drugs like bemcentinib, everolimus, talazoparib, and others for potential approaches to targeting these mutations.

The serine/threonine kinase 11 (STK11) gene encodes the liver kinase B1 (LKB1) protein, an intracellular serine-threonine kinase with important roles in cellular metabolism, cell polarity, regulation of apoptosis, and the DNA damage response.1

Alterations in STK11 have been found in 3.04% of all cancers, with lung adenocarcinoma most strongly represented (13%) followed by breast invasive ductal carcinoma, non–small cell lung cancer (NSCLC), colon adenocarcinoma, and adenocarcinoma of unknown primary.1,2

Cancers such as cervical, gastrointestinal, and lung may also have STK11 alterations.1

STK11 was first recognized as a tumor suppressor gene in the late 1990s, but the mechanisms of oncogenicity due to loss-of-function mutations in STK11 remain under investigation.2

Alterations in STK11 can lead to loss of mTOR and hypoxia-inducible factor-1α (HIF-1α) regulation mediated by adenosine monophosphate–activated protein kinase (AMPK).2

Loss of LKB1 due to inactivating mutations in STK11 results in greater HIF-1α protein expression; this, in turn, shifts glucose metabolism to the glycolytic pathway to maintain energy supply.