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Related Experiment Videos

Novel antifolate drugs.

W Thomas Purcell1, David S Ettinger

  • 1The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Bunting-Blaustein Cancer Research Building, 1650 Orleans Street, Room G92, Baltimore, MD 21231-1000, USA. purceto@jhmi.edu

Current Oncology Reports
|February 14, 2003
PubMed
Summary
This summary is machine-generated.

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Antimetabolites, like methotrexate, are key cancer drugs. New antifolate agents are being developed to overcome drug resistance and improve cancer treatment efficacy and safety.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Antimetabolites are crucial chemotherapeutic agents for various cancers.
  • Folate antagonists, purine analogues, and pyrimidine analogues constitute the main antimetabolite categories.
  • Methotrexate, a prominent folate antagonist, targets dihydrofolate reductase, impacting nucleotide and amino acid synthesis.

Purpose of the Study:

  • To review enzymatic targets for antifolates.
  • To describe mechanisms of antifolate resistance.
  • To summarize the development of novel antifolate agents.

Main Methods:

  • Review of existing literature on antifolate mechanisms and resistance.
  • Analysis of clinical pharmacology of novel antifolate agents.

Related Experiment Videos

  • Examination of toxicity profiles and mitigation strategies.

    • Main Results:

    • Methotrexate resistance arises from mechanisms like reduced transport and gene amplification.
    • Several novel antifolate agents (e.g., pemetrexed, raltitrexed) are in development.
    • Folic acid and vitamin B12 supplementation can reduce pemetrexed toxicity without compromising efficacy.

    Conclusions:

    • Antifolate drug development aims to overcome resistance mechanisms.
    • Novel antifolates exhibit unique clinical pharmacology and varying developmental stages.
    • Optimizing antifolate therapy involves understanding resistance and managing toxicity.