Related Experiment Video

Updated: Jul 23, 2026

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
09:19

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo

Published on: February 6, 2015

Molecular features that predict the response to antimetabolite chemotherapies

Mahya Mehrmohamadi1,2,3,4, Seong Ho Jeong4, Jason W Locasale1,2,3

  • 1Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710 USA.

Cancer & Metabolism
|October 14, 2017
PubMed
Abstract

Insights

This study reveals that metabolic pathways targeted by chemotherapy drugs like 5-FU and Gemcitabine are specifically linked to patient treatment response, challenging the idea of non-specific cytotoxic effects.

Area of Science:

  • Oncology
  • Molecular Biology
  • Computational Biology

Background:

  • Antimetabolite chemotherapies targeting cellular metabolism are standard cancer treatments.
  • Patient responses to these therapies vary significantly, with underlying reasons largely unknown.

Purpose of the Study:

  • To develop a computational method for identifying gene expression signatures related to chemotherapy response.
  • To investigate the determinants of sensitivity to 17 antimetabolite agents.

Main Methods:

  • A novel computational approach was used to identify gene expression signatures.
  • Analysis was performed on human tumors and cancer cell lines.
  • Seventeen antimetabolite agents were characterized across various contexts.

Main Results:

  • Distinct gene expression signatures associated with favorable and unfavorable responses to 5-fluorouracil (5-FU) and Gemcitabine were identified.
  • Metabolic pathways directly targeted by these antimetabolites showed specific enrichment in their respective expression signatures.
  • Evidence suggests that antimetabolite drugs do not solely rely on non-specific cytotoxic mechanisms.

Conclusions:

  • Unbiased analyses indicate that the activity of specific metabolic pathways plays a significant role in therapeutic response to antimetabolite chemotherapy.
  • This finding supports a more targeted understanding of chemotherapy efficacy and patient heterogeneity.
Keywords:
5-fluorouracilAntimetabolite chemotherapiesGemcitabineMolecular determinants of response to chemotherapy

More Related Videos

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models09:58

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models

Published on: December 9, 2016

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype14:51

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype

Published on: June 17, 2022

Related Concept Videos

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 specific...
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...
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...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
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...
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...