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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...
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...
Combined Effects of Drugs: Synergism01:27

Combined Effects of Drugs: Synergism

Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists01:27

Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists

5-HT3 receptor antagonists, such as dolasetron, granisetron (Kytril), ondansetron (Zofran), and palonosetron (Axoli), are crucial in managing chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea. These drugs selectively block 5-HT3 receptors in the visceral vagal and spinal afferent nerves, chemoreceptor trigger zone, and the vomiting center. They have a rapid onset of action and can be given as a single dose before chemotherapy. Ondansetron and granisetron, in particular,...
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...
Anthelminthic Agents01:15

Anthelminthic Agents

Anthelmintic drugs differ significantly from antiparasitic therapies targeting protozoa, primarily due to differences in parasite biology. Whereas most protozoal treatments act on proliferating cells, anthelmintics are typically directed against mature, nonproliferative helminths. The therapeutic approach considers the helminth's reliance on neuromuscular coordination, glucose metabolism, and microtubular integrity for survival, reproduction, and localization within the host. Most anthelmintics...

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Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
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Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

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Pemetrexed disodium, a novel antifolate with multiple targets.

N J Curtin1, A N Hughes

  • 1University of Newcastle upon Tyne Medical School, Cancer Research Unit, UK. n.j.curtin@ncl.ac.uk

The Lancet. Oncology
|March 22, 2002
PubMed
Summary

Pemetrexed disodium is a potent antifolate drug effective against various cancers. Supplementing with dietary folate can reduce its toxicity, improving the therapeutic index for patients.

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Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Pemetrexed disodium is a novel antifolate agent.
  • It targets thymidylate synthase and purine synthesis enzymes, crucial for cell proliferation.
  • Cells resistant to other antifolates often show less resistance to pemetrexed.

Purpose of the Study:

  • To evaluate the efficacy and toxicity of pemetrexed in preclinical and clinical settings.
  • To investigate the role of dietary folate in modulating pemetrexed's therapeutic index.
  • To identify cancers responsive to pemetrexed as a single agent or in combination therapy.

Main Methods:

  • Preclinical studies using human tumor cell lines and xenografts.
  • Clinical trials assessing pemetrexed's activity and side effects.
  • Investigation into the impact of folate status on pemetrexed toxicity.

Main Results:

  • Pemetrexed demonstrated significant activity against non-small-cell lung cancer, head and neck squamous-cell carcinoma, colon, and breast cancer.
  • Neutropenia and gastrointestinal issues were the primary dose-limiting toxic effects.
  • Preclinical data and patient observations suggest dietary folate supplementation mitigates toxicity.

Conclusions:

  • Pemetrexed is an active antifolate agent with a broad spectrum of activity in various cancers.
  • Dietary folate supplementation is crucial for improving the therapeutic index and managing toxicity.
  • Pemetrexed, especially combined with cisplatin, shows promise in treating non-small-cell lung cancer and mesothelioma.