Proposed model for the SXR-mediated response to irinotecan in colon cancer cells. In LS180 cells, CPT-11 is metabolized to SN-38 by the carboxylesterases (CE). SN-38 induces the activation of SXR. Consequently, the transcription factor is recruited to the CYP3A4 and CYP3A5 promoter and upregulates the expression of these genes. SXR also constitutively activates MDR1 and MRP1 expression. As a feedback loop, CYP3A4, CYP3A5 and the transporters reduce the concentration of active irinotecan inside the cell, which favors cell proliferation. As a consequence, we propose that the combined detection of SXR together with a high expression of CYP3A4 should help to define in advance the subsets of tumors that will fail to respond to chemotherapy based on irinotecan treatment.