T

Therapeutic efficacy ^

Fig. 6.20 The effect of hyperforin on irinotecan therapy. Source: Adapted with permission from Meijerman et al., Oncologist 2006.

Hyperforin, binds to and activates X receptor (PXR). Upon activation, PXR forms a heterodimer with the 9-cis retinoic acid receptor (RXR), and this complex binds to the xenobiotic response elements (PXRE) in the CYP3A4 gene. The transcription of the gene is increased, and more CYP3A4 id formed, thereby increasing the metabolism of irinoetcan into an inactive metabolite, oxidized irinotecan. The amount of irinotecan left to be metabolized into SN-38 decreases, leaving less active SN-38 and lower therapeutic efficacy of irinotecan.

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