Related Experiment Video

Updated: May 26, 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

TFAP2E-DKK4 and chemoresistance in colorectal cancer

Matthias P A Ebert1, Marc Tänzer, Benjamin Balluff

  • 1Department of Medicine II, Universitätsmedizin Mannheim, Ruprecht-Karls-Universität Heidelberg, Mannheim, Germany. matthias.ebert@umm.de

The New England Journal of Medicine
|January 6, 2012
PubMed
Abstract

Insights

Transcription factor AP-2 epsilon (TFAP2E) hypermethylation predicts poor response to chemotherapy in colorectal cancer. Targeting dickkopf homolog 4 protein (DKK4) may overcome this drug resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Predictors of chemotherapy response in advanced colorectal cancer are lacking.
  • Alterations in transcription factor AP-2 epsilon (TFAP2E) and dickkopf homolog 4 protein (DKK4) are implicated in cancer and chemotherapy resistance.
  • TFAP2E and DKK4 roles in colorectal cancer chemotherapy response require further investigation.

Purpose of the Study:

  • To evaluate TFAP2E and DKK4 as predictors of colorectal cancer response to chemotherapy.
  • To investigate the functional relationship between TFAP2E and DKK4 in chemotherapy resistance.

Main Methods:

  • Analysis of TFAP2E expression, methylation, and function in colorectal cancer cell lines and patient cohorts (total 294 patients).
  • Assessment of DKK4 overexpression and its impact on chemoresistance.
  • Correlation of TFAP2E hypermethylation with chemotherapy response.

Main Results:

  • TFAP2E was hypermethylated in 51% of patients, associated with decreased expression.
  • DKK4 overexpression in cell lines conferred resistance to fluorouracil but not irinotecan or oxaliplatin.
  • TFAP2E hypermethylation significantly predicted nonresponse to chemotherapy (P<0.001), with a 5.74-fold increased risk ratio for nonresponse.

Conclusions:

  • TFAP2E hypermethylation is a significant predictor of clinical nonresponsiveness to chemotherapy in colorectal cancer.
  • TFAP2E-mediated drug resistance is functionally linked to DKK4.
  • Targeting DKK4 presents a potential strategy to overcome TFAP2E-mediated chemotherapy resistance in colorectal cancer patients with TFAP2E hypermethylation.

More Related Videos

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure09:38

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib09:38

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Published on: June 26, 2019

Related Concept Videos

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...
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...
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
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...
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...