Related Experiment Video

Updated: Apr 15, 2026

Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells
10:28

Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells

Published on: January 10, 2018

8.8K

Molecular Pathways: GLI1-Induced Drug Glucuronidation in Resistant Cancer Cells

Hiba Ahmad Zahreddine1, Katherine L B Borden2

  • 1Institute of Research in Immunology and Cancer (IRIC), Department of Pathology and Cell Biology, Université de Montréal, Montreal, Quebec, Canada.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|March 27, 2015
PubMed

Insights

Overexpressed UDP-glucuronosyl transferase (UGT) enzymes in cancer promote drug resistance, contrary to previous beliefs. Inhibiting GLI1 can reverse this resistance, offering a new therapeutic strategy for various cancers.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Drug resistance is a major obstacle in developing effective cancer therapies.
  • Traditionally, reduced UDP-glucuronosyl transferase (UGT) activity was linked to cancer due to impaired carcinogen clearance.
  • This study explores a novel role for UGTs in cancer drug resistance.

Purpose of the Study:

  • To investigate the role of UDP-glucuronosyl transferase (UGT) enzymes in cancer multidrug resistance.
  • To identify the relationship between GLI1, UGTs, and drug resistance in acute myelogenous leukemia (AML).
  • To explore the clinical potential of targeting UGTs to overcome drug resistance.

Main Methods:

  • Analysis of UGT enzyme levels in AML patients at diagnosis versus relapse.
  • Investigating the effect of GLI1 inhibition on UGT levels and drug resistance.
  • Examining UGT-mediated drug resistance in other cancer types (colorectal, chronic lymphoblastic leukemia).

Main Results:

  • Increased UGT enzyme levels were observed in relapsed AML patients compared to diagnosis.
  • Elevated UGT levels correlated with resistance to ribavirin and cytarabine.
  • GLI1 inhibition reversed UGT overexpression and overcame drug resistance.
  • UGT overexpression was also implicated in resistance to Hsp90 inhibitors and vorinostat in other cancers.

Conclusions:

  • Overexpression of UGTs contributes to oncogenesis by promoting drug resistance, a newly identified mechanism.
  • Targeting GLI1 offers a potential clinical strategy to overcome UGT-mediated drug resistance.
  • UGT status may inform treatment choices for various cancers, highlighting differential drug metabolism in cancer cells.

More Related Videos

Author Spotlight: Innovative Cancer Therapies with Iron Oxide Nanoparticles for Glioblastoma Treatment09:02

Author Spotlight: Innovative Cancer Therapies with Iron Oxide Nanoparticles for Glioblastoma Treatment

Published on: September 27, 2024

3.2K

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...
3.9K
Phase II Reactions: Glucuronidation01:24

Phase II Reactions: Glucuronidation

Glucuronidation, a pivotal phase II biotransformation process, involves the coupling of glucuronic acid to a drug or xenobiotic. Given its widespread occurrence and critical role in drug metabolism, it's considered the most crucial phase II reaction. It enhances the water solubility of substances, aiding their expulsion from the body. The driving force behind these reactions is a group of enzymes known as UDP-glucuronosyltransferases (UGTs). UGTs facilitate the transfer of a glucuronic acid...
2.2K
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...
5.7K
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...
9.2K
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
78