While CIS combined with CB839 or with ERA delayed the tumor growth moderately compared to the CNTRL (green symbols, P <0.05, Fig. 6F), the triple combination (CB839+ERA+CIS) was able to overcome resistance to CIS, inducing a significant tumor growth delay (red symbol) comparing to treatments by CIS alone or two-drug combinations (¶ and §, Fig. 6F,P values specified in the caption). The gene discussed is ESR1; the disease is in situ carcinoma.