Unraveling the Role of STK11/LKB1 in Non-small Cell Lung Cancer

Abstract

There are two major groups of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLCs can be further separated into three different categories: lung adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Pulmonary adenocarcinomas represent nearly half of all lung cancer cases and are known to be caused by smoking, certain occupational exposures, and specific genetic mutations. Scientists have noticed that most NSCLCs are driven by defects in the following genes: EGFR, BRAF, ALK, MET, and HER. Abnormalities in the STK11/LKB1 gene have also been shown to induce lung adenocarcinoma. LKB1-deficient cancer cells contain an overactive AMPK "energy sensor," which inhibits cellular death and promotes glucose, lipid, and protein synthesis via the mTOR protein complex. Studies have also discovered that the loss of STK11/LKB1 favors oncogenesis by creating an immunosuppressive environment for tumors to grow and accelerate events such as angiogenesis, epithelial-mesenchymal transition (EMT), and cell polarity destabilization. STK11/LKB1-mutant lung cancers are currently treated with radiotherapy with or without chemotherapy. Recent clinical trials studying the effects of glutaminase inhibitors, mTOR inhibitors, and anti-PD-L1 therapy in lung cancer patients have yielded promising results. This narrative review provides an overview of the STK11/LKB1 gene and its role in cancer development. Additionally, a summary of the LKB1/APMK/mTOR is provided.

Prognostic value ofKRASmutations,TP53mutations and PD-L1 expression among lung adenocarcinomas treated with immunotherapy

“…This suggests that they may both independently play a role as predictors of a higher PD-L1 expression. In addition, studies have also found a correlation between STK11 wild-type and PD-L1 expression and that loss of function in STK11 may yield a more aggressive cancer 18 20 32. However, no significant association for STK11 mutations and PD-L1 expression was found in the current study.…”

“…Approximately 30% of lung adenocarcinomas in Europe have a mutation in KRAS 13–15 and mutations in KRAS generally predict poor survival among patients with lung cancer 16 . KRAS mutations have been associated with smoking13 and they often co-occur with other oncogenic alterations, especially loss-of-function mutations in STK11 or TP53 17–20. Mutations in TP53 and KRAS have been associated with an increased expression of PD-L1 and TMB 21–26.…”

Recent progress in targeted therapy for non-small cell lung cancer

“…In the 1990s, STK11 (serine threonine kinase 11) was identified as a significant tumor suppressor gene (Sumbly and Landry, 2022). Clinical data show that a wide variety of tumors carry STK11/ LKB1 abnormalities (Sumbly and Landry, 2022).…”

“…In the 1990s, STK11 (serine threonine kinase 11) was identified as a significant tumor suppressor gene (Sumbly and Landry, 2022). Clinical data show that a wide variety of tumors carry STK11/ LKB1 abnormalities (Sumbly and Landry, 2022). STK11 encodes liver kinase B1 (LKB1), a protein kinase important in maintaining cellular energy balance (Sumbly and Landry, 2022).…”

Radioresistance of Non-Small Cell Lung Cancers and Therapeutic Perspectives

“…Some co-mutations occur frequently with KRAS mutations. One of these mutations, the STK11 mutation has been reported to induce resistance of NSCLCs to treatment and stem-cell-like properties [ 50 ] and might be also a target of interest.…”