title: Targeting the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway: an emerging treatment strategy for squamous cell lung carcinoma.
abstract: Squamous cell lung carcinoma accounts for approximately 30% of all non-small cell lung cancers (NSCLCs). Despite progress in the understanding of the biology of cancer, cytotoxic chemotherapy remains the standard of care for patients with squamous cell lung carcinoma, but the prognosis is generally poor. The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is one of the most commonly activated signaling pathways in cancer, leading to cell proliferation, survival, and differentiation. It has therefore become a major focus of clinical research. Various alterations in the PI3K/AKT/mTOR pathway have been identified in squamous cell lung carcinoma and a number of agents targeting these alterations are in clinical development for use as single agents and in combination with other targeted and conventional treatments. These include pan-PI3K inhibitors, isoform-specific PI3K inhibitors, AKT inhibitors, mTOR inhibitors, and dual PI3K/mTOR inhibitors. These agents have demonstrated antitumor activity in preclinical models of NSCLC and preliminary clinical evidence is also available for some agents. This review will discuss the role of the PI3K/AKT/mTOR pathway in cancer and how the discovery of genetic alterations in this pathway in patients with squamous cell lung carcinoma can inform the development of targeted therapies for this disease. An overview of ongoing clinical trials investigating PI3K/AKT/mTOR pathway inhibitors in squamous cell lung carcinoma will also be included.
authors.affiliation: Highlands Oncology Group, 3232 North Hills Boulevard, Fayetteville, AR 72703, USA. Electronic address: tbeck@hogonc.com.
authors.forename: Joseph Thaddeus
authors.initials: JT
authors.lastname: Beck
authors.affiliation: University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR 72205, USA. Electronic address: aismail@uams.edu.
authors.forename: Amen
authors.initials: A
authors.lastname: Ismail
authors.affiliation: University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR 72205, USA. Electronic address: ctolomeo@uams.edu.
authors.forename: Christina
authors.initials: C
authors.lastname: Tolomeo
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology*; D002986:Clinical Trials as Topic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D058990:Molecular Targeted Therapy; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human
keywords: Biomarkers; PI3K inhibitor; PI3K/AKT/mTOR pathway; Squamous cell lung carcinoma; mTOR inhibitor