Related Experiment Video

Updated: Jun 9, 2025

Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres
06:52

Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres

Published on: July 22, 2020

6.5K

GPA33 expression in colorectal cancer can be induced by WNT inhibition and targeted by cellular therapy

Teresa Börding1, Tobias Janik1, Philip Bischoff1,2,3

  • 1Institute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

Oncogene
|October 30, 2024
PubMed

Insights

GPA33 is a target for colorectal cancer (CRC) therapy, but expression varies. Inhibiting WNT signaling boosts GPA33, enhancing CAR T-cell therapy effectiveness against CRC tumors.

Area of Science:

  • Oncology
  • Immunotherapy
  • Molecular Biology

Background:

  • GPA33 is a surface antigen expressed in colorectal cancer (CRC), showing potential for targeted therapy.
  • Previous clinical trials targeting GPA33 in CRC have yielded suboptimal response rates.
  • Understanding GPA33 expression dynamics and regulation is crucial for improving CRC treatment strategies.

Purpose of the Study:

  • To investigate GPA33 expression patterns and regulation in colorectal cancer.
  • To develop and evaluate GPA33-targeted cellular therapy for CRC.
  • To identify strategies for enhancing GPA33 expression and therapeutic efficacy.

Main Methods:

  • GPA33 expression analysis in CRC cohorts using immunohistochemistry and immunofluorescence.
  • In vitro and in vivo investigation of GPA33 regulation via oncogenic signaling interference.
  • Engineering and assessment of anti-GPA33-CAR T cells for CRC treatment.

Main Results:

  • Consistent intratumoral heterogeneity of GPA33 expression was observed in CRC, with antigen loss at tumor edges and metastatic sites.
  • GPA33-positive cells exhibited a differentiated phenotype and low WNT pathway activity.
  • Downregulation of WNT activity increased GPA33 expression in vitro and in GPA33-negative subpopulations.
  • GPA33-CAR T cells demonstrated activation and reduced xenograft growth upon intratumoral application.

Conclusions:

  • GPA33 expression in CRC is heterogeneous and linked to WNT pathway activity and tumor progression.
  • Simultaneous WNT inhibition may enhance GPA33 expression, improving GPA33-targeted therapies.
  • GPA33 represents a promising target for cellular immunotherapy in colorectal cancer.

More Related Videos

In vitro Organoid Culture of Primary Mouse Colon Tumors07:33

In vitro Organoid Culture of Primary Mouse Colon Tumors

Published on: May 17, 2013

35.0K
Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies09:29

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

Published on: September 30, 2016

13.6K

Related Concept Videos

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...
6.2K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.7K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.2K
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...
7.5K