Targeting non-small cell lung cancer: Molecular mechanisms and clinical studies (Review).

Over the past two decades, notable advances have been made in the treatment of non-small cell lung cancer (NSCLC), as well as in the elucidation of molecular mechanisms and the development of novel therapeutics (for example, targeted therapy and immunotherapy), whose clinical benefits have been documented. The epidermal growth factor receptor and anaplastic lymphoma kinase are well-known tumor targets; both can promote tumor growth through PI3K/AKT/mTOR pathway. Other oncogenes and tumor suppressor genes such as Kirsten rat sarcoma and tumor protein 53 have also been investigated. The notable immune checkpoints are programmed cell death protein-1/programmed cell death ligand-1 and cytotoxic T-lymphocyte-associated protein 4. However, the overall survival rate of patients with NSCLC is still low due to primary or acquired drug resistance, which is associated with abnormal signaling pathways. In particular, patients with advanced disease who have non-druggable targets or lack an immune response have a poor prognosis, such as the mutation of serine/threonine kinase 11, also known as liver kinase B1 (LKB1). LKB1 impacts cellular energy metabolism and the tumor immune microenvironment, resulting in little benefit from current therapies. Therefore, further research into more effective treatments is warranted to potentially improve the outcomes of patients with NSCLC in the future.