Supplementary Materials

Supplementary Material for:

Synergistic action of the MCL-1 inhibitor S63845 with current therapies in preclinical models of triple-negative and HER2-amplified breast cancer

Delphine Merino, James R. Whittle, François Vaillant, Antonin Serrano, Jia-Nan Gong, Goknur Giner, Ana Leticia Maragno, Maïa Chanrion, Emilie Schneider, Bhupinder Pal, Xiang Li, Grant Dewson, Julius Gräsel, Kevin Liu, Najoua Lalaoui, David Segal, Marco J. Herold, David C. S. Huang, Gordon K. Smyth, Olivier Geneste, Guillaume Lessene, Jane E. Visvader,* Geoffrey J. Lindeman*

*Corresponding author. Email: visvader{at}wehi.edu.au (J.E.V.); lindeman{at}wehi.edu.au (G.J.L.)

Published 2 August 2017, Sci. Transl. Med. 9, eaam7049 (2017)
DOI: 10.1126/scitranslmed.aam7049

This PDF file includes:

  • Materials and Methods
  • Fig. S1. Expression of BCL-2 family members and sensitivity to S63845 or A-1210477.
  • Fig. S2. RNA-seq analysis of BCL-2 family members in PDX models.
  • Fig. S3. Expression of BCL-XL, BCL-2, BCL-W, and MCL-1 in METABRIC and TCGA databases.
  • Fig. S4. Characterization of ER, PR, HER2, and BCL-2 family member protein expression in PDX models by immunohistochemistry.
  • Fig. S5. Deep sequencing of genome-wide lentiviral sgRNA libraries, knockdown of BH3 proteins, and S63845-mediated disruption of MCL-1 complexes containing BH3-only proteins.
  • Fig. S6. Generation and analysis of S63845-resistant cell lines.
  • Fig. S7. Exploring molecular mechanisms of resistance to S63845.
  • Fig. S8. Effect of concomitant treatment of SK-BR-3 cells with a BH3 mimetic and trastuzumab, lapatinib, or docetaxel.
  • Fig. S9. Role of BIM in the synergistic effect of S63845.
  • Fig. S10. Individual tumor growth curves in TNBC and HER2-amplified PDXs after combination treatment with S63845 and docetaxel or trastuzumab.
  • Fig. S11. Effect of combination therapy on tumor cell death.
  • Fig. S12. Effect of combination therapy on mouse weight, biochemistry, and blood counts.
  • Table S1. Clinical, histopathological, and molecular features of primary breast tumors.
  • References (5366)

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Other Supplementary Material for this manuscript includes the following:

  • Table S2 (Microsoft Excel format). BCL-2 family mRNA expression in PDX models.
  • Table S3 (Microsoft Excel format). Statistical analysis of gene expression between different molecular subtypes of breast cancer in PDX models.
  • Table S4 (Microsoft Excel format). Statistical analysis of MCL-1, BCL-2, BCL-XL, and BCL-W gene expression between different molecular subtypes of breast cancer in METABRIC and TCGA data sets.
  • Table S5 (Microsoft Excel format). Normalized sgRNA counts up-regulated in S63845-treated cells compared to DMSO control.
  • Table S6 (Microsoft Excel format). Primers used for sequencing CRISPR clones.
  • Table S7 (Microsoft Excel format). Sequencing analysis of CRISPR clones for BAK, BAX, BMF, and NOXA.

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