Extended Data Table 4. Top 15 downregulated and top 15 upregulated pathways in sensitive tumors treated with PT2399.
| Ingenuity Canonical Pathways | Molecules | P-Value |
|---|---|---|
| Top 15 Downregulated pathways | ||
| Cell Cycle Control of
Chromosomal Replication |
CDC7,ORC1,MCM7,CDC45,MCM2,CDK2,ORC6,MCM3,MCM6,MCM4,MCM5,CDC6 | 7.94328E-16 |
| Mitotic Roles of Polo-Like Kinase | KIF23,ESPL1,PRC1,CDC20,CCNB2,PPP2R2A,CDC7,PLK4,PTTG1,PLK1,CDK1,CCNB1,FBXO5 | 3.98107E-12 |
| Cell Cycle: G2/M DNA Damage Checkpoint Regulation |
TOP2A,BRCA1,AURKA,CKS1B,CKS2,CCNB2,PLK1,CDK1,CCNB1 | 2.51189E-08 |
| Cyclins and Cell Cycle Regulation | CCNE2,SUV39H1,CCND1,CDK2,E2F1,CCNA2,CCNB2,PPP2R2A,CDK1,CCNB1 | 1.31826E-07 |
| ATM Signaling | JUN,BLM,BRCA1,FANCD2,CDK2,RAD51,CCNB2,CDK1,CCNB1 | 1.38038E-07 |
| GADD45 Signaling | CCNE2,BRCA1,CCND1,CDK2,CDK1,CCNB1 | 1.77828E-07 |
| DNA damage-induced 14-3-3σ Signaling | CCNE2,BRCA1,CDK2,CCNB2,CDK1,CCNB1 | 1.77828E-07 |
| Estrogen-mediated S-phase Entry | CCNE2,CCND1,CDK2,E2F1,CCNA2,CDK1 | 8.31764E-07 |
| Role of BRCA1 in DNA Damage Response |
BLM,BRCA1,FANCB,FANCD2,E2F1,FANCA,BRCA2,RAD51,PLK1 | 1.58489E-06 |
| Hereditary Breast Cancer Signaling | BLM,BRCA1,FANCB,FANCD2,CCND1,E2F1,FANCA,BRCA2,RAD51,CDK1,CCNB1 | 1.8197E-06 |
| Role of CHK Proteins in Cell Cycle Checkpoint Control |
BRCA1,CDK2,E2F1,CLSPN,PPP2R2A,PLK1,CDK1 | 1.20226E-05 |
| Ovarian Cancer Signaling | BRCA1,VEGFA,SUV39H1,LEF1,PTGS2,CCND1,E2F1,PRKAG2,BRCA2,RAD51 | 1.65959E-05 |
| Pancreatic Adenocarcinoma Signaling | VEGFA,SUV39H1,PTGS2,CCND1,BIRC5,CDK2,E2F1,BRCA2,RAD51 | 1.99526E-05 |
| Aryl Hydrocarbon Receptor Signaling | JUN,CCNE2,MCM7,CCND1,IL1A,CDK2,E2F1,CCNA2,IL6,ALDH1A3 | 2.29087E-05 |
| Small Cell Lung Cancer Signaling | CCNE2,SUV39H1,PTGS2,CCND1,CDK2,E2F1,CKS1B | 6.45654E-05 |
| Top 15 Upregulated pathways | ||
| Hepatic Fibrosis / Hepatic Stellate
Cell Activation |
COL19A1,COL4A6,FGFR2,IGFBP4,TGFB3,MYL4,PDGFD,COL21A1,MYL3,IGF1 | 8.13E-06 |
| Axonal Guidance Signaling | GLIS2,CXCL12,BMP5,MYL4,PDGFD,EPHB3,SRGAP3,SMO,SEMA3F,IGF1,ADAMTS1,SEMA3G,BMP4, MYL3 |
2.09E-05 |
| Human Embryonic Stem Cell Pluripotency |
FGFR2,TGFB3,BMP5,PDGFD,BMP4,LEFTY2,SMO | 0.000145 |
| PAK Signaling | MYL4,PDGFD,EPHB3,MYLK,MYL3 | 0.001 |
| Basal Cell Carcinoma Signaling | GLIS2,BMP5,BMP4,SMO | 0.00302 |
| RhoA Signaling | MYL4,MYLK,SEMA3F,MYL3,IGF1 | 0.00389 |
| Agranulocyte Adhesion and Diapedesis | CXCL12,MYL4,MYL3,CCL11,CXCL14,MMP24 | 0.004266 |
| Cellular Effects of Sildenafil (Viagra) | MYL4,ADCY5,MYLK,MYL3,PDE5A | 0.004467 |
| TR/RXR Activation | THRSP,HIF1A,G6PC,AKR1C1/AKR1C2 | 0.00631 |
| Regulation of Actin-based Motility by Rho | DIRAS3,MYL4,MYLK,MYL3 | 0.006918 |
| Factors Promoting Cardiogenesis
in Vertebrates |
TGFB3,BMP5,BMP4,SMO | 0.007413 |
| CXCR4 Signaling | DIRAS3,CXCL12,MYL4,ADCY5,MYL3 | 0.010233 |
| Cardiomyocyte Differentiation via
BMP Receptors |
BMP5,BMP4 | 0.011482 |
| Cardiac Hypertrophy Signaling | DIRAS3,TGFB3,MYL4,ADCY5,MYL3,IGF1 | 0.012303 |
| Molecular Mechanisms of Cancer | DIRAS3,TGFB3,BMP5,BCL2L11,BMP4,ADCY5,HIF1A,SMO | 0.013183 |