Related Experiment Video

Updated: Jan 23, 2026

An Affordable HIV-1 Drug Resistance Monitoring Method for Resource Limited Settings
19:57

An Affordable HIV-1 Drug Resistance Monitoring Method for Resource Limited Settings

Published on: March 30, 2014

19.1K

Drug metabolizing enzymes-associated chemo resistance and strategies to overcome it

Himanshu Verma1, Malkeet Singh Bahia2, Shalki Choudhary1

  • 1MolecularModelling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University , Patiala , India.

Drug Metabolism Reviews
|June 18, 2019
PubMed

Insights

Drug resistance in cancer is a major challenge. This review highlights how drug metabolizing enzymes (DMEs) cause chemoresistance by rapidly breaking down anti-cancer drugs, impacting treatment efficacy.

Area of Science:

  • Pharmacology
  • Oncology
  • Biochemistry

Background:

  • Cancer remains a leading cause of mortality globally, despite ongoing research into novel chemotherapies.
  • Tumor cells rapidly develop drug resistance, significantly hindering the progress of effective anti-cancer drug development.
  • Drug metabolizing enzymes (DMEs) represent an often-overlooked mechanism contributing to chemoresistance through accelerated drug metabolism.

Purpose of the Study:

  • To review the role of DMEs in pharmacokinetic resistance and chemoresistance.
  • To elucidate the molecular mechanisms underlying DME-associated chemoresistance.
  • To discuss inhibitors and strategies for overcoming DME-mediated drug resistance in cancer therapy.

Main Methods:

  • Literature review focusing on DMEs involved in cancer drug metabolism and resistance.
  • Analysis of molecular mechanisms of DME-associated chemoresistance.
  • Compilation of current strategies and inhibitors targeting DMEs for adjuvant cancer therapy.

Main Results:

  • Identified key DMEs (e.g., ALDH1A1, GST-π, DPD, CYP1B1) implicated in metabolizing anti-cancer drugs.
  • Demonstrated how rapid drug metabolism by DMEs diminishes the efficacy of chemotherapeutic agents.
  • Highlighted the underutilization of DME inhibition as a therapeutic strategy.

Conclusions:

  • DMEs play a critical role in chemoresistance by reducing the effective concentration of anti-cancer drugs.
  • Inhibitors of DMEs show potential as adjuvant therapies to enhance chemotherapy effectiveness.
  • Further research and clinical application of strategies targeting DMEs are warranted to combat cancer drug resistance.
Keywords:
ALDHCYP450CancerDMEsDPDGSTNQO1UGTdrug resistance

More Related Videos

Advancements in the Metabolic Profiling of Three-Dimensional Brain Tumor Spheroids for Drug Screening06:50

Advancements in the Metabolic Profiling of Three-Dimensional Brain Tumor Spheroids for Drug Screening

Published on: September 5, 2025

422
Author Spotlight: Characterizing Novel Enzymes from Extremophiles and Common Pathogens to Understand DNA Repair and Replication05:33

Author Spotlight: Characterizing Novel Enzymes from Extremophiles and Common Pathogens to Understand DNA Repair and Replication

Published on: July 5, 2024

1.3K

Related Concept Videos

Drug Metabolism: Phase I Reactions01:17

Drug Metabolism: Phase I Reactions

A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar,...
4.7K
Drug Metabolism: Phase II Reactions01:14

Drug Metabolism: Phase II Reactions

Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
4.9K
Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses...
199
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
2.4K
Enzymes02:34

Enzymes

Inside living organisms, enzymes act as catalysts for many biochemical reactions involved in cellular metabolism. The role of enzymes is to reduce the activation energies of biochemical reactions by forming complexes with its substrates. The lowering of activation energies favor an increase in the rates of biochemical reactions.
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
93.9K
Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug01:14

Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug

In pharmacotherapy, monitoring drug concentrations is paramount, especially for drugs whose therapeutic effects hinge on both the active compound and its metabolite. Hepatic impairment profoundly influences drug potency by altering liver function. If the drug is more potent than its metabolite, impaired liver function amplifies drug activity due to elevated drug concentration levels. Conversely, if the metabolite holds greater potency, diminished liver function diminishes drug activity by...
220