Background: Cancer cells use several mechanisms to resist the cytotoxic effects of drugs, resulting in
tumor progression and invasion. One such mechanism capitalizes on the body's natural defense against xenobiotics
by increasing the rate of xenobiotic efflux and metabolic inactivation. Xenobiotic metabolism typically involves
conversion of parent molecules to more soluble and easily excreted derivatives in reactions catalyzed by Phase I and
Phase II drug metabolizing enzymes.
Methods: We performed a structured search of peer-reviewed literature on P450 (CYP) 3A, with a focus on
CYP3A4 and CYP3A5.
Results: Recent reports indicate that components of the xenobiotic response system are upregulated in some diseases,
including many cancers. Such components include the pregnane X receptor (PXR), CYP3A4 and CYP3A5
enzymes. The CYP3A enzymes are a subset of the numerous enzymes that are transcriptionally activated following
the interaction of PXR and many ligands.
Conclusion: Intense research is ongoing to understand the functional ramifications of aberrant expression of these
components in diseased states with the goal of designing novel drugs that can selectively target them.