biostudies-literatureTorres-Ayuso PIntramural NIH HHSNCIFundacion Ramon Areces postdoctoral fellowshipNCI NIH HHSNational Institute for General Medical SciencesNIGMS NIH HHSNIH NCI1411-1423https://www.ebi.ac.uk/biostudies/studies/S-EPMC8178189biostudies-literatureUnknown11(6)Lung squamous cell carcinoma (LSCC) is the second most prevalent type of lung cancer. Despite extensive genomic characterization, no targeted therapies are approved for the treatment of LSCC. Distal amplification of the 3q chromosome is the most frequent genomic alteration in LSCC, and there is an urgent need to identify efficacious druggable targets within this amplicon. We identify the protein kinase TNIK as a therapeutic target in LSCC. <i>TNIK</i> is amplified in approximately 50% of LSCC cases. TNIK genetic depletion or pharmacologic inhibition reduces the growth of LSCC cells <i>in vitro</i> and <i>in vivo</i>. In addition, TNIK inhibition showed antitumor activity and increased apoptosis in established LSCC patient-derived xenografts. Mechanistically, we identified the tumor suppresCancer discoveryTNIK Is a Therapeutic Target in Lung Squamous Cell Carcinoma and Regulates FAK Activation through Merlin.PMC81781891ZIABC011691-01ZIA BC01169175N91019D00024R01 GM102262Andresson TRobinson CMTurk BERitt DADas SBensen RCMorrison DKSpecht SIRies ALGouker BAn ETorres-Ayuso PDifilippantonio SLiang RJCachau REBassel LBrognard JNyswaner KMKarim BOMiller CJfalseTNIK Is a Therapeutic Target in Lung Squamous Cell Carcinoma and Regulates FAK Activation through Merlin.Lung squamous cell carcinoma (LSCC) is the second most prevalent type of lung cancer. Despite extensive genomic characterization, no targeted therapies are approved for the treatment of LSCC. Distal amplification of the 3q chromosome is the most frequent genomic alteration in LSCC, and there is an urgent need to identify efficacious druggable targets within this amplicon. We identify the protein kinase TNIK as a therapeutic target in LSCC. <i>TNIK</i> is amplified in approximately 50% of LSCC cases. TNIK genetic depletion or pharmacologic inhibition reduces the growth of LSCC cells <i>in vitro</i> and <i>in vivo</i>. In addition, TNIK inhibition showed antitumor activity and increased apoptosis in established LSCC patient-derived xenografts. Mechanistically, we identified the tumor suppres2021-01-01T00:00:00Z2021 Jun2026-05-08T18:24:12.762Z2022-02-11T13:20:51.343ZS-EPMC81781893349519710.1158/2159-8290.CD-20-079710.1158/2159-8290.cd-20-0797