Colorectal cancer (CRC) is one of the most common malignancies and causes of cancer-related deaths worldwide. CRC has been found to be primarily sporadic in nature and may be in part related to lifestyle risk factors such as lack of exercise, obesity, alcohol consumption, and tobacco smoking. CRC is an etiologically heterogeneous disease that is characterized by tumor-sidedness related to its embryologic origin, and molecular alterations known as mutations in global gene expression. Studies have found that the cumulative impact of genetic and epigenetic mutations in tumor suppressor genes, oncogenes, and DNA mismatch repair genes may be a potential precursor to the onset of the disease as well as its progression.
Germline mutations in the APC gene and DNA mismatch-repair genes including MLH1 have been highlighted to play a key role in the etiology of CRC and result in a predisposition to the disease in some families. Genetic alterations have been found to influence the dysregulation of signaling pathways which lead to drug resistance, inhibition of apoptosis, and progress of invasion and proliferation leading to colorectal tumor progression and metastasis. Somatic mutations of EGFR-1 signal transduction pathway genes, especially of the RAS family and BRAF kinases, as well as of ERK/MAPK, appear to be important in tumorigenesis and cancer progression. In addition, alterations in the PI3K/AKT/mTOR pathway especially of PI3K and PTEN also appear to play an important role in CRC development and progression.
Until recently it has been very difficult to follow the development and implications of such mutations as well as their relationship to disease outcomes, due to the risks of repeated biopsies to obtain new tissue. The advent of “liquid biopsies” with the ability to analyze nanogram amounts of circulating cell-free tumor DNA (cfDNA / ctDNA) has made it possible to follow patients’ disease course and correlate it with molecular changes. Recent studies have shown a correlation between CRC disease outcomes and the emergence of new mutations of EGFR-1 signaling pathway genes with a relationship between higher mutant allele frequency and poorer patient outcomes. In addition, emergent mutations of the extracellular ligand-binding domain may negatively affect the binding of anti-
EGFR-1 monoclonal antibodies to specific epitopes in this domain.
This Research Topic aims to generate a discussion regarding the emergence of mutations of various components of the EGFR-1 signaling pathway in the field of colorectal cancer, how it influences the disease, and the impact it has on patient outcomes. We welcome Original Research, Reviews, Systematic Reviews, and Mini-Reviews.
Please note: Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of the scope of this section and will not be accepted as part of this Research Topic.
Colorectal cancer (CRC) is one of the most common malignancies and causes of cancer-related deaths worldwide. CRC has been found to be primarily sporadic in nature and may be in part related to lifestyle risk factors such as lack of exercise, obesity, alcohol consumption, and tobacco smoking. CRC is an etiologically heterogeneous disease that is characterized by tumor-sidedness related to its embryologic origin, and molecular alterations known as mutations in global gene expression. Studies have found that the cumulative impact of genetic and epigenetic mutations in tumor suppressor genes, oncogenes, and DNA mismatch repair genes may be a potential precursor to the onset of the disease as well as its progression.
Germline mutations in the APC gene and DNA mismatch-repair genes including MLH1 have been highlighted to play a key role in the etiology of CRC and result in a predisposition to the disease in some families. Genetic alterations have been found to influence the dysregulation of signaling pathways which lead to drug resistance, inhibition of apoptosis, and progress of invasion and proliferation leading to colorectal tumor progression and metastasis. Somatic mutations of EGFR-1 signal transduction pathway genes, especially of the RAS family and BRAF kinases, as well as of ERK/MAPK, appear to be important in tumorigenesis and cancer progression. In addition, alterations in the PI3K/AKT/mTOR pathway especially of PI3K and PTEN also appear to play an important role in CRC development and progression.
Until recently it has been very difficult to follow the development and implications of such mutations as well as their relationship to disease outcomes, due to the risks of repeated biopsies to obtain new tissue. The advent of “liquid biopsies” with the ability to analyze nanogram amounts of circulating cell-free tumor DNA (cfDNA / ctDNA) has made it possible to follow patients’ disease course and correlate it with molecular changes. Recent studies have shown a correlation between CRC disease outcomes and the emergence of new mutations of EGFR-1 signaling pathway genes with a relationship between higher mutant allele frequency and poorer patient outcomes. In addition, emergent mutations of the extracellular ligand-binding domain may negatively affect the binding of anti-
EGFR-1 monoclonal antibodies to specific epitopes in this domain.
This Research Topic aims to generate a discussion regarding the emergence of mutations of various components of the EGFR-1 signaling pathway in the field of colorectal cancer, how it influences the disease, and the impact it has on patient outcomes. We welcome Original Research, Reviews, Systematic Reviews, and Mini-Reviews.
Please note: Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of the scope of this section and will not be accepted as part of this Research Topic.
