Strategies to Overcome or Circumvent P-Glycoprotein Mediated Multidrug Resistance

Abstract

Cancer patients who receive chemotherapy often experience intrinsic or acquired resistance to a broad spectrum of chemotherapeutic agents. The phenomenon, termed multidrug resistance (MDR), is often associated with the over-expression of P-glycoprotein, a transmembrane protein pump, which can enhance efflux of a various chemicals structurally unrelated at the expense of ATP depletion, resulting in decrease of the intracellular cytotoxic drug accumulation. The MDR has been a big threaten to the human health and the war fight for it continues. Although several other mechanisms for MDR are elucidated in recent years, considerable efforts attempting to inverse MDR are involved in exploring P-glycoprotein modulators and suppressing P-glycoprotein expression. In this review, we will report on the recent advances in various strategies for overcoming or circumventing MDR mediated by P-glycoprotein.

Targeted Delivery of Doxorubicin by Folic Acid-Decorated Dual Functional Nanocarrier

“…36 Various mechanisms have been identified that are involved in the different types and/or stages of cancers. 37,38 One primary mechanism involves the overexpression of P-glycoprotein (P-gp), which plays a vital role in the development of multiple drug resistance (MDR). 39−43 P-gp, a member of ATP-binding cassette transporter, is one of the major drug efflux transporters and increased expression of P-gp leads to decreased drug accumulation in multidrug-resistant cells and the development of resistance to anticancer drugs.…”

An improved d-α-tocopherol-based nanocarrier for targeted delivery of doxorubicin with reversal of multidrug resistance

“…Various mechanisms have been identified that are involved in the different types and/or stages of cancers [35,36]. One major mechanism involves the overexpression of P-glycoprotein (P-gp), which plays an important role in developing multiple drug resistance (MDR) [37].…”

Nanomedicine therapeutic approaches to overcome cancer drug resistance

“…Their lack of specificity requires a large dose to achieve clinical inhibition and thus results in toxicity. Numerous modifications of these inhibitors have appeared as promising candidates, but clinical trials continue to fail [113]. However, the use of these molecules in relation to nanomedicines is still an attractive strategy due to increased targeting and accumulation.…”