OCT 14, 2021 3:00 AM PDT

Mechanism of Resistance to Colorectal Cancer Treatment Uncovered

WRITTEN BY: Katie Kokolus

Colorectal cancer develops when a series of changes occur across multiple genes.  While researchers have paid significant attention to understanding these changes, identifying the precise alterations leading to colorectal cancer remains an essential question in cancer research. 

Researchers at the University of Birmingham recently published a paper in Proceedings of the National Academy of Sciences, which identified a gene mutation associated with tumor growth in murine models of colorectal cancer and a poor prognosis in colorectal cancer patients.

The study utilized the  APCmin/+ strain of mice.  APCmin/+ is a well-validated murine model mimicking early-stage colorectal cancer.   When scientists deleted a protein called tetraspanin-6 (Tspan6) in the mice, tumors grew more rapidly.  Thus, in mouse models, Tspan6 suppressed the early stages of colorectal cancer development.

To translate this discovery into a clinical application, the investigators also examined Tspan6 in samples from patients with colorectal cancer.  Immunohistochemistry analysis revealed that colorectal cancer patients with high levels of Tspan6 had a better clinical prognosis associated with significantly longer survival.  

The study also investigated the impact of Tspan6 on therapeutic efficacy of a standard colorectal cancer treatment, a monoclonal antibody called cetuximab.  Cetuximab is a drug used to treat certain types of colorectal cancer, which express the protein epidermal growth factor receptor (EGFR). Overexpression of EGRF leads to constant activation of pathways promoting cell division. Therefore, in many cancer types, including colorectal cancer, EGFR directly promotes tumor growth.  

Cetuximab inhibits EGFR-driven tumor growth by binding EGFR on cancer cells and prevents further growth.  Although cetuximab is efficacious for some patients, many colorectal cancer patients develop a resistance to the treatment. 

A biomarker that could predict which patients would benefit most from the drug could make instrumental advances in personalized medicine.  Notably, the patients examined in the study indicated that Tspan6 did indeed correlate with response to cetuximab.

The results of this study are impactful in multiple ways.  First, this study demonstrates that Tspan6 regulates colorectal cancer development, and its absence could indicate high-risk individuals and encourage them to seek regular cancer screening.  Additionally, Tspan6 could be a predictive biomarker to help doctors and patients make better treatment choices. 

Sources: Proceedings of the National Academy of Sciences, APCmin/+, Immunohistochemistry, cetuximab, EGFR

About the Author
  • PhD in Tumor Immunology. I am interested in developing novel strategies to improve the efficacy of immunotherapies used to extend cancer survivorship.
You May Also Like
AUG 18, 2021
Cannabis Sciences
Cancer Patients Use Less Cannabis than General Public
AUG 18, 2021
Cancer Patients Use Less Cannabis than General Public
Despite increasing legalization for recreational cannabis across the US, cancer patients have largely abstained from usi ...
AUG 19, 2021
Cancer
Japanese Berry Vine Could Treat Lung Cancer
AUG 19, 2021
Japanese Berry Vine Could Treat Lung Cancer
A berry-producing vine in Japan has shown promise in mouse models for treating lung cancer. The corresponding study was ...
AUG 29, 2021
Cancer
Blood Test over 90% Accurate in Detecting Lung Cancer
AUG 29, 2021
Blood Test over 90% Accurate in Detecting Lung Cancer
An AI-powered blood test was able to correctly detect the presence of lung cancer over 90% of the time in patient sample ...
SEP 13, 2021
Cancer
Fat Loss can Predict Gastric Cancer Survival
SEP 13, 2021
Fat Loss can Predict Gastric Cancer Survival
Cancer cachexia is a metabolic disorder in cancer patients experiencing uncontrolled weight loss.  While cancer cac ...
SEP 22, 2021
Cancer
Whole Genome Sequencing for Cancer Diagnostics
SEP 22, 2021
Whole Genome Sequencing for Cancer Diagnostics
The human genome consists of genetic material known as DNA.  We all have unique DNA sequences made up of four bases ...
OCT 11, 2021
Cancer
Different Cancer Types Metastasize to Specific Regions of the Brain
OCT 11, 2021
Different Cancer Types Metastasize to Specific Regions of the Brain
Metastatic cancer occurs when cancer spreads from its original site of origin to a distant location in the body. Wh ...
Loading Comments...