Abstract
Colorectal cancer (CRC) is a predominant malignancy worldwide, being the fourth most common cause of mortality and morbidity. The CRC incidence in adolescents, young adults, and adult populations is increasing every year. In the pathogenesis of CRC, various factors are involved including diet, sedentary life, smoking, excessive alcohol consumption, obesity, gut microbiota, diabetes, and genetic mutations. The CRC tumor microenvironment (TME) involves the complex cooperation between tumoral cells with stroma, immune, and endothelial cells. Cytokines and several growth factors (GFs) will sustain CRC cell proliferation, survival, motility, and invasion. Epidermal growth factor receptor (EGFR), Insulin-like growth factor -1 receptor (IGF-1R), and Vascular Endothelial Growth Factor -A (VEGF-A) are overexpressed in various human cancers including CRC. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) and all the three major subfamilies of the mitogen-activated protein kinase (MAPK) signaling pathways may be activated by GFs and will further play key roles in CRC development. The main aim of this review is to present the CRC incidence, risk factors, pathogenesis, and the impact of GFs during its development. Moreover, the article describes the relationship between EGF, IGF, VEGF, GFs inhibitors, PI3K/AKT/mTOR-MAPK signaling pathways, and CRC.
Highlights
If, in 1950, colorectal cancer (CRC) was a rare malignancy, today, it became a predominant form worldwide [1]
In 2015, Baena R and co-workers published the results of the epidemiologic studies from EMBASE and PubMed-NCBI, carried out since November 2014, and revealed that obesity increases the risk of CRC by 19%, while regular physical activity reduces this risk by 24%
The CRC pathogenesis is very complex and assumes the presence of many genetic mutations that will be involved in cancer progression
Summary
In 1950, colorectal cancer (CRC) was a rare malignancy, today, it became a predominant form worldwide [1]. CRC is the third most common cancer, and the incidence is increasing with age [5,6,7]. Since 1994, the CRC incidence in adolescents and young adults under 45 years has been increasing every year [10,11,12,13]. The statistical data published in 2014 revealed that 26% of proximal colon cancers were diagnosed in women younger than 50 years, while 56% of the cases were registered in women aged 80 years and older [14]. Kim SE reported that women are more prone to developing right-sided (proximal) colon cancer compared with men. For early CRC, the 5-year survival rate is ~90%, but this rate decreases to 15% in the case of mCRC [22]
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