PDF file - 20K, Gene notations and ABI assay identifiers.

PDF file - 51K, Figitumumab potency in 93 cell lines annotated by normalized mRNA expression of selected IGF pathway genes.

PF-06463922 is well tolerated in mice.

PF-06463922 is potent against ALK-mutated NB cell lines in vitro. Mean (n=3) IC50 values ({plus minus} SD) for crizotinib and PF-06463922 are listed for 10 NB cell lines harboring the indicated ALK aberrations, plus one NSCLC cell line (NCI-H3122). Fold increases in the IC50 values with crizotinib over those measured for PF-06463922 are also listed in the right-most column.

XLS file, 129K, Description of gene expression experiments from Table 2S for analysis in R.

XLS file, 361K, Normalized NanoString expression values used in the analysis.

PDF file - 33K, Figitumumab sensitivity gene target correlates rank ordered by statistical significance and annotated with false discovery rates and chromosomal positions of gene locations.

XLS file, 53K, Target sequences NanoString assays.

PDF file - 23K, Summary of figitumumab potency in selected cell lines in vitro and tumor growth inhibition for cell lines growth as subcutaneous tumor xenografts.

Table S1. Statistics for the crystallographic analysis; Table S2. Biochemical and cellular potencies of the second generation CDK-directed drug AG-024322; Table S3. In vitro analysis of binding potency of abemaciclib, dinaciclib, and palbociclib to non-kinase proteins; Table S4. Broad kinase selectivity of selective CDK4/6 drugs; Table S5. Biochemical dose-response follow-up was conducted for a subset of kinases inhibited by the three CDK4/6 drugs using a Km concentration of ATP (Carna Biosciences) (CDK proteins excluded); Table S6. Kinase selectivity toward endogenous human kinases using irreversible ATP analog target engagement assay; Table S7. Biochemical potencies of selective CDK4/6 drugs palbociclib (PD-0332991); Table S8. Human pharmacokinetic properties of CDK-targeted drugs; Table S9. Isothermal titration calorimetry results for CDK-directed drugs binding to CDK6 in the absence of cyclin D.

PDF file - 312K, DLDA gene expression classifier.

PDF file, 166K, Figure 1S. Differentially expressed genes between most sensitive and resistant models; Figure 2SA. Top genes differentially modulated gene between CC1599 and the remaining models; Figure 2SB. Unsupervised of cell cycle gene modulation after treatment; Figure 3S. Plots of correlation between gene modulation after treatment and baseline expression; Figure 4S. Correlation between modulation after treatment and TGI; Figure 5S. Correlation between TGI and Notch-10 score. Comparison between the Notch-10 score and tumor growth inhibition.

Detailed description of the methods used in the manuscript

PDF file, 208K, Methods for NanoString gene analysis.

PDF file - 266K, Single agent and combination activity of figitumumab and correlation of combination synergy with the genetic status of major cancer drivers or RNA expression of cancer drivers and IGF pathway alterations.

In vivo effects of crizotinib and PF-06463922 on event-free survival (EFS) in neuroblastoma PDX and xenograft models.

In vivo efficacy studies comparing PF-06463922 treatment at 10 mg/kg/day (5 mg/kg BID) and 3 mg/kg/day (1.5 mg/kg BID) with crizotinib treatment at 100 mg/kg QD in: A, Felix-PDX xenografts and B, SH-SY5Y xenografts.

PDF file - 64K, Supplementary summary of performance of DLDA gene expression signature classifiers across cell lines including cell line classification and mean number of genes in classifier and including classifier compositions rank ordered by t value.