Abstract
Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death. Most cases of CRC are detected in Western countries, with its incidence increasing year by year. The probability of suffering from colorectal cancer is about 4%–5% and the risk for developing CRC is associated with personal features or habits such as age, chronic disease history and lifestyle. In this context, the gut microbiota has a relevant role, and dysbiosis situations can induce colonic carcinogenesis through a chronic inflammation mechanism. Some of the bacteria responsible for this multiphase process include Fusobacterium spp, Bacteroides fragilis and enteropathogenic Escherichia coli. CRC is caused by mutations that target oncogenes, tumour suppressor genes and genes related to DNA repair mechanisms. Depending on the origin of the mutation, colorectal carcinomas can be classified as sporadic (70%); inherited (5%) and familial (25%). The pathogenic mechanisms leading to this situation can be included in three types, namely chromosomal instability (CIN), microsatellite instability (MSI) and CpG island methylator phenotype (CIMP). Within these types of CRC, common mutations, chromosomal changes and translocations have been reported to affect important pathways (WNT, MAPK/PI3K, TGF-β, TP53), and mutations; in particular, genes such as c-MYC, KRAS, BRAF, PIK3CA, PTEN, SMAD2 and SMAD4 can be used as predictive markers for patient outcome. In addition to gene mutations, alterations in ncRNAs, such as lncRNA or miRNA, can also contribute to different steps of the carcinogenesis process and have a predictive value when used as biomarkers. In consequence, different panels of genes and mRNA are being developed to improve prognosis and treatment selection. The choice of first-line treatment in CRC follows a multimodal approach based on tumour-related characteristics and usually comprises surgical resection followed by chemotherapy combined with monoclonal antibodies or proteins against vascular endothelial growth factor (VEGF) and epidermal growth receptor (EGFR). Besides traditional chemotherapy, alternative therapies (such as agarose tumour macrobeads, anti-inflammatory drugs, probiotics, and gold-based drugs) are currently being studied to increase treatment effectiveness and reduce side effects.
Highlights
A sedentary lifestyle is related with obesity, another important risk factor for colorectal cancer. This increased risk is linked to both food intake and increased levels of visceral adipose tissue (VAT), a hormonally active component of total body fat that can promote the development of colorectal cancer through the secretion of proinflammatory cytokines, which leads to an inflammatory situation in the colon and rectum, insulin resistance and modulation of metabolic enzymes such as adiponectin or lectin [18]
The pathogenic mechanisms leading to this situation can be included in three different pathways, namely chromosomal instability (CIN), microsatellite instability (MSI) and CpG island methylator phenotype (CIMP)
We have reviewed the latest discoveries in the study of Colorectal cancer (CRC) research, as well as the newest findings in diagnostic and treatment methodologies in order to provide researchers and clinicians with an updated vision of the key insights into this disease
Summary
Colorectal cancer (CRC) is one of the most common cancers worldwide, with between one and Ctowlormeciltlaiolncnaenwcecras(eCsRbCei)ngisdioangenoosfedtheveemryoysetarc,otmhums monakcinagncCeRrCs twheorthldirwd imdoes,twcoimthmboentwcaenecner one and twanodmthilelifoonurnthewmocsatsceosmbmeionngcaduiasegnofocsaendceerv-reerlyateydeadre,atthhu, swmitha7k0in0,g00C0 RdCeatthhseptehrirydeamr, oexscteceodmedmon canceronalnydbythleunfogu, lritvhermaonsdt sctoommamchoncacnacuersse. The incidence of CRC has risen by more than. 200,000 new cases per year from 1990 to 2012. Most cases of CRC are detected in Western countries (55%), but this tendency is changing due to the fast development of some countries over the past few. Only 33% of all CRC-related deaths in the world occur in Western countries in 2010 [8] thanks to the improvements made in health systems and the implementation of screening programs. Predictions for 2016 are not encouraging at all, with 134,490 new cases of colorectal cancer and 49,190 deaths related to this cancer expected
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