Supplementary Materials

The PDF file includes:

  • Fig. S1. Control experiments for competition experiments done with isogenic ccRCC cell lines treated with CDK4/6 inhibitors.
  • Fig. S2. The CDK4/6 inhibitor palbociclib preferentially inhibits pVHL-deficient cells in various ccRCC cell lines.
  • Fig. S3. Changes in proliferation of ccRCC cells after pVHL reconstitution does not account for differential sensitivity to CDK4/6 inhibition.
  • Fig. S4. Individual knockdown of CDK4 or CDK6 does not differentially affect the viability of ccRCC cells based on VHL status.
  • Fig. S5. PT2399 attenuates palbociclib-induced up-regulation of cyclin D1 abundance in HIF-2α–dependent, but not HIF-2α–independent, cell lines.
  • Fig. S6. Effect of palbociclib, PT2399, and their combination on cyclin D1 and phospho-pRb abundance in vivo.
  • Fig. S7. Growth of ccRCC orthotopic xenografts during treatment with vehicle, palbociclib, PT2399, or their combination.
  • Fig. S8. Growth of HIF-2α inhibition–resistant VHL-null ccRCC orthotopic xenografts during treatment with vehicle, palbociclib, or the combination of palbociclib with PT2399.
  • Fig. S9. Antitumor activity of abemaciclib in VHL-null ccRCC orthotopic xenografts.
  • Fig. S10. Antitumor activity of palbociclib and abemaciclib in a ccRCC PDX model.
  • Fig. S11. Schematic of analogous signaling mechanisms in breast cancer and ccRCC.
  • Table S1. sgRNA oligonucleotides.
  • Table S2. PCR primers.
  • Legends for data files S1 to S3

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Other Supplementary Material for this manuscript includes the following:

  • Data file S1 (Microsoft Excel format). Results of screen for synthetic lethality with vhl inactivation using dsRNA library in Drosophila cells.
  • Data file S2 (Microsoft Excel format). Results of screen for synthetic lethality with VHL inactivation using chemical library in human 786-O and UMRC-2 ccRCC cells.
  • Data file S3 (Microsoft Excel format). Overlap between genes encoding targets of chemicals that scored in chemical screen and human orthologs of Drosophila genes that scored in dsRNA screen.