Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

2.6K
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...
2.6K
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

94
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...
94
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

81
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...
81

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Factors Associated With Pancreatectomy Among Australians With Pancreatic Cancer: A Population-Based Study.

ANZ journal of surgery·2026
Same author

Stakeholder Consensus Selection of Data Elements and Indicators for a Pancreatic Cancer Surgical Outcomes Registry in Australia and Aotearoa New Zealand: Modified Delphi Process.

ANZ journal of surgery·2026
Same author

An Indolent Enteropathy Accelerated by Combination Immune Checkpoint Inhibitor Therapy.

ACG case reports journal·2026
Same author

Ultra-sensitive detection of mutant <i>KRAS</i> in circulating tumor DNA predicts survival in resectable pancreatic adenocarcinoma.

Frontiers in oncology·2026
Same author

Paediatric and Adult Solid Tumours Exhibiting NTRK Gene Fusions in Australia, 2020-2044: A Population-Based Statistical Modelling Study.

Cancer medicine·2026
Same author

Treatment Timeliness in Extensive-Stage SCLC and Impact on Survival: A Registry-Based Observational Study.

JTO clinical and research reports·2026
Same journal

Phase 2 Dose Expansion Trial of OBI-3424, a DNA-Alkylating Prodrug, in Patients with Advanced Solid Tumors Expressing AKR1C3.

The oncologist·2026
Same journal

Divergent Biology and Outcomes of Somatic Transformations in Germ Cell Tumors.

The oncologist·2026
Same journal

Modernizing Disease Assessment in Prostate Cancer Trials: The Prostate Cancer Working Group 4 Framework.

The oncologist·2026
Same journal

Use of liposomal irinotecan with 5-FU and oxaliplatin (NALIRIFOX) in neoadjuvant pancreatic adenocarcinoma: NEO-Nal-IRI trial.

The oncologist·2026
Same journal

Dose-Expansion Study of OBI-999, a Globo H-Targeting Antibody-Drug Conjugate, in Patients with Advanced Solid Tumors.

The oncologist·2026
Same journal

Comparison of Allo-HSCT outcomes after CAR-T therapy versus chemotherapy in pediatric patients with relapsed/refractory B-ALL: a retrospective study.

The oncologist·2026
See all related articles

Related Experiment Video

Updated: May 4, 2026

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

14.5K

ECOG-ACRIN E6293: Phase II Study of Raltitrexed in Advanced Colorectal Cancer.

Chengwei Peng1, Paul Catalano2, John Zalcberg3,4

  • 1Division of Hematology/Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center Northwestern University, Chicago, IL, 60611, United States.

The Oncologist
|February 20, 2026
PubMed
Summary
This summary is machine-generated.

Raltitrexed, a direct thymidylate synthase (TS) inhibitor, showed limited efficacy in advanced colorectal cancer (CRC) patients. This phase II trial found no significant response rates, suggesting raltitrexed is not a viable treatment option for CRC.

Keywords:
antifolate inhibitioncolorectal cancerraltitrexed

More Related Videos

Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
08:12

Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer

Published on: March 14, 2019

6.1K
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
10:27

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

Published on: July 25, 2020

8.0K

Related Experiment Videos

Last Updated: May 4, 2026

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

14.5K
Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
08:12

Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer

Published on: March 14, 2019

6.1K
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
10:27

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

Published on: July 25, 2020

8.0K

Area of Science:

  • Oncology
  • Clinical Trials
  • Pharmacology

Background:

  • Thymidylate synthase (TS) inhibition is a key strategy for colorectal cancer (CRC) treatment.
  • 5-Flurouracil (5-FU) is an indirect TS inhibitor commonly used in CRC regimens.
  • Raltitrexed, a direct TS inhibitor, was investigated for potentially improved efficacy and toxicity in CRC.

Purpose of the Study:

  • To evaluate the efficacy and safety of raltitrexed in patients with advanced colorectal cancer (CRC).
  • To assess raltitrexed's effectiveness across different patient strata based on prior 5-FU treatment.
  • To explore the prognostic value of thymidylate synthase (TS) expression as a biomarker.

Main Methods:

  • A phase II ECOG-ACRIN trial enrolled 101 advanced CRC patients from December 1995 to December 1998.
  • Patients were stratified based on prior treatment: 5-FU naïve, 5-FU without leucovorin, or 5-FU with leucovorin.
  • Raltitrexed 3 mg/m² was administered every 3 weeks; primary endpoints included Objective Response Rate (ORR) and toxicity.

Main Results:

  • The overall Objective Response Rate (ORR) for raltitrexed was low across all strata, with no significant differences observed.
  • Median Progression-Free Survival (mPFS) and median Overall Survival (mOS) were limited, with the highest mOS observed in the 5-FU naïve group (14.5 months).
  • The trial did not advance to stage two due to low ORR; TS expression as a biomarker yielded inconclusive results.

Conclusions:

  • Raltitrexed demonstrated limited efficacy and did not achieve significant response rates in patients with advanced CRC.
  • The study concluded that TS expression was not a reliable biomarker for predicting raltitrexed response in this patient population.
  • No new safety concerns were identified with raltitrexed treatment in this phase II trial.