Colorectal cancer remains one of the most common cancers worldwide with low survival rates and poor prognosis. The 5-year survival rate for colorectal cancer is approximately 60% but becomes significantly reduced to an estimate of 10-12% for metastatic colorectal cancer (mCRC). Therefore, further studies are awaited to develop effective treatment. Primary treatment for localized colorectal cancer patients involves surgical approaches combined with chemotherapy and radiotherapy. In the metastatic setting treatment include chemotherapy and/or targeted therapies such as antiangiogenic agents, Epithelial Growth Factor Receptor (EGFR) inhibitors, BRAF inhibitors, human epidermal growth factor receptor 2 (HER2) inhibitors, immune checkpoint inhibitors, or NTRK (neurotrophic tyrosine receptor kinase) inhibitors.
Angiogenesis is a tightly regulated process that is mediated by a group of angiogenic factors such as vascular endothelial growth factor and its receptors. Antiangiogenic agents such as Bevacizumab and Aflibercept are widely used in combination with first and second line chemotherapy for mCRC. Studies have demonstrated EGFR as a molecular target as it has been found to play a key role in tumorigenesis, which activates various intracellular signaling pathways, including RAS-RAF-MAP kinase (MAPK) pathway and the PI3K-PTEN-Akt pathway, which then causes the activation of various transcription factors, which control gene expression for cell proliferation, migration and differentiation.
Studies have found EGFR to be overexpressed in colorectal cancer patients. This led to two anti-EGFR antibodies, cetuximab and panitumumab for metastatic colorectal cancer patients. More recent studies highlighted the overexpression of HER2 in metastatic colorectal cancer. HER2 has been found to affect the downstream activation of the MAPK and PI3K-PTEN-Akt pathway and therefore, triggers the activation of pro-survival signaling pathways in tumors. Clinical studies have also suggested that HER2 can influence resistance to anti-EGFR antibodies. Monoclonal antibodies including trastuzumab and pertuzumab or tyrosine kinase inhibitors can be used for the treatment of colorectal cancer with HER2 overexpression. Encorafenib (Braftovi®) is an oral small molecule BRAF inhibitor used in combination with cetuximab for the treatment of adult patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, who have received prior systemic therapy. Actionable gene fusions such as Neurotrophic Tropomyosin Receptor Kinases (NTRK) rearrangements are rare but might represent a new target to improve outcomes in this setting.
The aim of this Research Topic is to generate a discussion on how molecular targets can be utilized towards the treatment of metastatic colorectal cancer patients to improve the survival rate and prognosis. We welcome Original Research, Reviews, Systematic Reviews and Mini-Reviews. Papers on how to identify specific molecular targets for CRC as well as studies on the clinical or pre-clinical validations of the promising targets are particularly welcome.
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 scope for this section and will not be accepted as part of this Research Topic.
Colorectal cancer remains one of the most common cancers worldwide with low survival rates and poor prognosis. The 5-year survival rate for colorectal cancer is approximately 60% but becomes significantly reduced to an estimate of 10-12% for metastatic colorectal cancer (mCRC). Therefore, further studies are awaited to develop effective treatment. Primary treatment for localized colorectal cancer patients involves surgical approaches combined with chemotherapy and radiotherapy. In the metastatic setting treatment include chemotherapy and/or targeted therapies such as antiangiogenic agents, Epithelial Growth Factor Receptor (EGFR) inhibitors, BRAF inhibitors, human epidermal growth factor receptor 2 (HER2) inhibitors, immune checkpoint inhibitors, or NTRK (neurotrophic tyrosine receptor kinase) inhibitors.
Angiogenesis is a tightly regulated process that is mediated by a group of angiogenic factors such as vascular endothelial growth factor and its receptors. Antiangiogenic agents such as Bevacizumab and Aflibercept are widely used in combination with first and second line chemotherapy for mCRC. Studies have demonstrated EGFR as a molecular target as it has been found to play a key role in tumorigenesis, which activates various intracellular signaling pathways, including RAS-RAF-MAP kinase (MAPK) pathway and the PI3K-PTEN-Akt pathway, which then causes the activation of various transcription factors, which control gene expression for cell proliferation, migration and differentiation.
Studies have found EGFR to be overexpressed in colorectal cancer patients. This led to two anti-EGFR antibodies, cetuximab and panitumumab for metastatic colorectal cancer patients. More recent studies highlighted the overexpression of HER2 in metastatic colorectal cancer. HER2 has been found to affect the downstream activation of the MAPK and PI3K-PTEN-Akt pathway and therefore, triggers the activation of pro-survival signaling pathways in tumors. Clinical studies have also suggested that HER2 can influence resistance to anti-EGFR antibodies. Monoclonal antibodies including trastuzumab and pertuzumab or tyrosine kinase inhibitors can be used for the treatment of colorectal cancer with HER2 overexpression. Encorafenib (Braftovi®) is an oral small molecule BRAF inhibitor used in combination with cetuximab for the treatment of adult patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, who have received prior systemic therapy. Actionable gene fusions such as Neurotrophic Tropomyosin Receptor Kinases (NTRK) rearrangements are rare but might represent a new target to improve outcomes in this setting.
The aim of this Research Topic is to generate a discussion on how molecular targets can be utilized towards the treatment of metastatic colorectal cancer patients to improve the survival rate and prognosis. We welcome Original Research, Reviews, Systematic Reviews and Mini-Reviews. Papers on how to identify specific molecular targets for CRC as well as studies on the clinical or pre-clinical validations of the promising targets are particularly welcome.
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 scope for this section and will not be accepted as part of this Research Topic.