What Are the Challenges in Targeting P-glycoprotein?
Targeting P-gp in cancer therapy faces several challenges. First, the non-specific nature of many P-gp inhibitors can lead to systemic toxicity since P-gp is also expressed in normal tissues like the liver, kidney, and intestine. Second, cancer cells can develop compensatory mechanisms, such as upregulating other drug efflux transporters, thereby maintaining their resistant phenotype. Finally, the genetic and phenotypic heterogeneity of tumors complicates the development of universally effective P-gp inhibitors.
