Supplementary Materials

Supplementary Material for:

Rational combination therapy with PARP and MEK inhibitors capitalizes on therapeutic liabilities in RAS mutant cancers

Chaoyang Sun,* Yong Fang, Jun Yin, Jian Chen, Zhenlin Ju, Dong Zhang, Xiaohua Chen, Christopher P. Vellano, Kang Jin Jeong, Patrick Kwok-Shing Ng, Agda Karina B. Eterovic, Neil H. Bhola, Yiling Lu, Shannon N. Westin, Jennifer R. Grandis, Shiaw-Yih Lin, Kenneth L. Scott, Guang Peng, Joan Brugge, Gordon B. Mills

*Corresponding author. Email: csun5{at}mdanderson.org

Published 31 May 2017, Sci. Transl. Med. 9, eaal5148 (2017)
DOI: 10.1126/scitranslmed.aal5148

This PDF file includes:

  • Materials and Methods
  • Fig. S1. PARPi and MEKi induce inverse adaptive responses.
  • Fig. S2. Long-term assay of combination therapy with PARPi and MEKi demonstrates that low doses of drugs show synergy in OVCAR8 cells.
  • Fig. S3. PARPi plus MEKi/ERKi demonstrate synergy in cells with RAS mutations.
  • Fig. S4. Synergistic effects of PARP and MEK/ERK inhibition are lineage-independent and observed with KRAS/NRAS/BRAF mutations.
  • Fig. S5. RAS/ERK pathway activity is associated with HR competence, DNA damage checkpoints, and apoptotic sensitivity.
  • Fig. S6. MEKis decrease HR competence and enhance DNA damage induced by IR or PARPi.
  • Fig. S7. PARP and MRE11, but not FOXM1, contribute to the synergistic effects of PARPi and MEKi.
  • Fig. S8. PARPi, MEKi, and combination therapy have no effect on the body weight of mice.
  • References (53, 54)

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