Related Experiment Video

Updated: Feb 24, 2026

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

7.6K

An Update on Circumventing Multidrug Resistance in Cancer by Targeting P-Glycoprotein

Xiaoqian Yang1, Xiaoduan Li1, Zhenfeng Duan2

  • 1Department of Gynecology, Shanghai First Maternity and Infant Hospital affiliated Tongji University, Shanghai 201204, China.

Current Cancer Drug Targets
|August 19, 2017
PubMed
Abstract

Insights

Multidrug resistance in cancer, often caused by P-glycoprotein (Pgp), limits chemotherapy. While Pgp inhibitors show promise for overcoming resistance, current clinical trials have yielded disappointing results.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Multidrug resistance (MDR) is a significant challenge in cancer chemotherapy.
  • Overexpression of P-glycoprotein (Pgp) is a primary mechanism reducing intracellular drug accumulation in resistant cancer cells.
  • Pgp is a key target for overcoming chemotherapy resistance, but clinical outcomes with Pgp inhibitors have been poor.

Purpose of the Study:

  • To review the link between Pgp and drug resistance in cancer.
  • To update strategies for overcoming Pgp-mediated drug resistance, focusing on recent in vitro and in vivo advancements.
  • To discuss methods for establishing laboratory models of drug-resistant cancer.

Main Methods:

  • Literature review and analysis of current research on Pgp and drug resistance.
  • Examination of in vitro and in vivo studies investigating Pgp-targeting strategies.
  • Discussion of methodologies for creating drug-resistant cancer models.

Main Results:

  • Currently available Pgp inhibitors are unsuitable for clinical reversal of drug resistance due to their physiological roles in detoxification.
  • Pgp inhibitors tested in clinical trials at laboratory doses have not improved outcomes for cancer patients.
  • Compounds targeting Pgp are recognized for their potential in circumventing drug resistance.

Conclusions:

  • Direct clinical application of current Pgp inhibitors to reverse established resistance is not effective.
  • Further research is needed to develop effective Pgp-targeting strategies for clinical use.
  • Targeting Pgp remains a promising avenue for future cancer treatment strategies to combat drug resistance.
Keywords:
Multidrug resistanceP-glycoproteinP-glycoprotein inhibitordrug resistant models establishment.

More Related Videos

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure09:38

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

9.2K
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?14:20

Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?

Published on: June 13, 2014

17.2K

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.8K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.0K
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
68
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
6.2K
Carrier-Mediated Transport01:06

Carrier-Mediated Transport

Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
1.4K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
45