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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...
Treatment Resistent Cancers02:56

Treatment Resistent 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...
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...

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Related Experiment Video

Updated: Jul 13, 2026

Rapid Identification of Chemical Genetic Interactions in Saccharomyces cerevisiae
12:13

Rapid Identification of Chemical Genetic Interactions in Saccharomyces cerevisiae

Published on: April 5, 2015

Resistance to 5-fluorouracil

R M Mader1, M Müller, G G Steger

  • 1Department of Clinical Pharmacology, Vienna University School of Medicine, Austria. robert.mader@akh-wien.ac.at

General Pharmacology
|November 11, 1998
PubMed
Summary

Overcoming resistance to 5-fluorouracil (5-FU) chemotherapy is crucial for treating cancers like colorectal cancer. Research is exploring multifactorial resistance mechanisms to improve treatment strategies.

Area of Science:

  • Oncology
  • Cancer Chemotherapy
  • Pharmacology

Background:

  • Primary and secondary resistance to 5-fluorouracil (5-FU) is a significant challenge in cancer chemotherapy.
  • 5-FU remains a primary treatment for colorectal cancer, making resistance circumvention critical.

Purpose of the Study:

  • To investigate the multifactorial nature of fluoropyrimidine resistance.
  • To identify key events contributing to 5-FU resistance in vivo beyond thymidylate synthase.
  • To explore novel parameters for predicting and overcoming 5-FU resistance.

Main Methods:

  • Evaluation of (fluoro)pyrimidine converting enzymes.
  • Analysis of the mutational status of apoptosis regulators.
  • Assessment of tumor angiogenesis.

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Main Results:

  • Resistance to 5-FU involves complex factors including transport, metabolism, apoptosis, and cell cycle kinetics.
  • Current clinical prediction of 5-FU resistance is limited, primarily focusing on thymidylate synthase.
  • Preclinical studies offer insights into resistance circumvention, but clinical trial confirmation is rare.

Conclusions:

  • A deeper understanding of in vivo 5-FU resistance mechanisms is needed.
  • Investigating additional parameters like enzyme activity, apoptosis regulators, and angiogenesis is essential.
  • New insights can guide the development of improved therapeutic strategies beyond current schedules.