Abstract

<p>Supplementary Figure 1: Characterization of INX-315. Supplementary Figure 2: Effect of INX-315 and PF-07104091 on viability of cancer and non-malignant cell lines. Supplementary Figure 3: Effect of INX-315 on cell cycle in CCNE1-amplified cancer cell lines. Supplementary Figure 4: Further characterization of the effects of INX-315 in in vitro and in vivo models of CCNE1-amplified cancer. Supplementary Figure 5: Effects of INX-315 treatment on gene expression in models of CCNE1amplified ovarian carcinoma. Supplementary Figure 6: Characterization of CDK4/6 inhibitor-resistant cell lines. Supplementary Figure 7: Response of CDK4/6 inhibitor-resistant breast cancer cells to INX-315 and PF-07104091. Supplementary Figure 8: Effects of INX-315 and PF-07104091 on CDK4/6 inhibitor-resistant breast cancer cells. Supplementary Figure 9: Impact of INX-315 +/- continued CDK4/6 inhibition in CDK4/6 inhibitorresistant breast cancer cells. Supplementary Figure 10: Characterization of a new mouse model of acquired CDK4/6 inhibitor resistance. Supplementary Figure 11: Effect of INX-315 on expression of senescence-related genes in CDK4/6 inhibitor-resistant breast cancer cells. Supplementary Figure 12: Epigenomic and transcriptomic features of INX-315 induced senescence in CDK4/6 inhibitor-resistant breast cancer. Supplementary Figure 13: Impact of INX-315 treatment of CDK4/6 inhibitor resistant breast cancer on expression of apoptosis and differentiation-related genes. Supplementary Figure 14: Impact of co-inhibition of CDK2 and CDK4/6 on cell cycle and development of CDK4/6 inhibitor resistance in breast cancer cells.</p>

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