Ribociclib

All animals used in this study were housed with a 12:12-h light-dark cycle and fed with a standard rodent diet and water in the pathogen-free animal facility at Charlie Norwood VA Medical Center. Animal experiments were conducted with a protocol approved by the Institutional Animal Care and Use Committee of Charlie Nor-wood VA Medical Center. Male C57BL/6 mice were purchased from Jackson Laboratory (Bar Harbor, ME). The proximal tubule-specific Pfkfb3 knockout mice were generated by crossing Pfkfb3^flox/flox mice^{19 (link)} with PEPCK-Cre mice^{20 (link)} as previously described.^{21 (link)} For cisplatin treatment, mice were administered with a dose of cisplatin (30 mg/kg i.p.) as previously described.^{22 (link),23 (link)} For CDK4 inhibition, Ribociclib (Chemietek, Indianapolis, IN) or vehicle solution were administered by oral gavage (150 mg/kg, dissolved in citrate buffer) four hours prior to cisplatin injection as described.^{15 (link)}

H650, H1155, HOP62, H661, H2342, H23, A427, A549, H292, H2122, H157, H1299, Calu-6, H1395, H1437, H322, HCC4006, Calu-3, H2170, H3122, H460, H226 and HCC2935 cells were provided by the Moffitt Lung Cancer Center of Excellence Cell Line Core and were cultured in RPMI 1640 media containing 10% FBS (complete RPMI). All cell lines tested negative for mycoplasma contamination and have been authenticated by STR analysis. OSI-906, ceritinib, CEP-37440, ribociclib (Chemietek), PF-573228, BI-D1870 (Selleckchem), Compound C (Sigma), FMK (Axon Medchem) and SL0101 (Millipore) were dissolved in DMSO (10 mM) and diluted in complete RPMI for use. The H157 cell line used in this study is reported in the International Cell Line Authentication Committee database of commonly misidentified cell lines. H157 was only used to demonstrate the range of sensitivity to ceritinib in a large, diverse set of lung cancer cell lines. The batch used in this study has been authenticated by STR analysis. Studies performed with fresh frozen primary patient lung tissue were approved by the institutional scientific review committee (H. Lee Moffitt Cancer Center & Research Institute). Written informed consent was obtained prior to sample collection.

Trametinib and binimetinib (MEK162) were purchased from LC Laboratories. Ribociclib (LEE011) was purchased from Chemietek. Palbociclib isethionate was purchased from Selleckchem. Drug stocks were dissolved in DMSO at 10 mM and stored at −20 °C.