Supplementary Figure 7 from Ultrasensitive Response Explains the Benefit of Combination Chemotherapy Despite Drug Antagonism

Supplemental Figure 7. Previously published CRISPR inhibition (A) and CRISPR activation (B) data shows log-normally distributed drug sensitivities across a heterogeneous tumor cell population. When heritable heterogeneity was induced via CRISPR inhibition or activation, cell populations had log-normally distributed sensitivities. A) Genome-wide CRISPR inhibition screen was performed in dCas9-KRAB expressing Pfeiffer cells (diffuse large B-cell lymphoma) treated with single agent rituximab (R), 4-H-cyclophosphamide (C), doxorubicin (H), and vincristine (O). B) Genome-wide CRISPR activation screen was performed in dCas9-VP64 expressing K562 cells (chronic myeloid leukemia) and treated with single agent 4-H-cyclophosphamide (C), doxorubicin (H), and vincristine (O). Data publicly available from Palmer et al. eLife (2019)9.