Cancer is a condition where cells proliferate uncontrollably [1,2]. It is the leading cause of death in economically developed countries and the second leading cause of death in developing countries [3]. Colorectal cancer (CRC) is the third most common cause of cancer death globally, with an estimated 2.2 million new cases and 1.1 million deaths expected over the next decade [4]. CRC accounts for 9.2% of cancer-related deaths, making it the second leading cause of cancer death [5,6,7]. Both genetic and environmental factors play a role in CRC causation [8]. Chronic colitis due to inflammatory bowel disease (IBD) is also associated with an increased risk of CRC [9]. CRC has a poor prognosis, and there is a critical need for new diagnostic and prognostic biomarkers to reduce CRC-related deaths [10,11]. Cytokine networks are largely involved in the prognosis and pathogenesis of CRC [12]. Tumors express cytokines with both antitumor and pro-tumor properties [13]. Cytokines’ ability to stimulate oncogenic signaling has shifted research focus towards their role in promoting cell proliferation and survival during tumorigenesis [14]. Immune cells activated in response to the tumor produce and release growth factors and cytokines to regulate the inflammatory environment in tumor tissues [15]. These inflammatory cytokines direct DNA damage in the epithelium [16]. They imply the pathogenesis and prognosis of CRC [12]. Interleukins have distinct roles in CRC progression through tumorigenesis [14] and are also involved in tumor growth, cancer cell invasion, and metastasis, while also inhibiting cancer through complex pathways [15]. In recent years, interleukins have gained significant attention due to their distinct roles in providing a new and promising strategy for CRC treatment [17].

Interestingly, interleukins are not the only biomarkers for CRC. Since the gut microbiome has been shown to play a crucial role in the development of CRC, several studies have investigated the use of gut microbes as biomarkers for CRC [18,19,20]. The presence of Fusobacterium nucleatum and Bacteroides fragilis in tumors has been reported in 43% and 24% of patients, respectively. The detection of these bacterial species has been found to correlate with the overall bacterial load, but further analysis of microbial signatures via diversity profiling suggests that their detection may be indicative of a specific microbial profile [21]. Consequently, the presence of F. nucleatum and clbA+ bacteria in stool samples can be used as a predictive marker for CRC with a relatively high specificity and moderate sensitivity [22]. It is important to note that these non-invasive screening approaches are still under development and more research is needed to validate their results in larger patient populations and confirm their efficacy compared to current screening methods. Several studies have also investigated the use of miRNA as biomarkers for CRC. For example, a study found that a panel of miRNAs (e.g., miR-21, miR-31, miR-146a, and miR-192) had a sensitivity and a specificity for detecting CRC [23]. Even though these studies demonstrate the potential of miRNA as a non-invasive biomarker for CRC, more research is still needed to validate these findings in larger patient populations [24,25,26]. The type of cancer and stage of the disease can impact the miRNA signature. Furthermore, the methods used to detect miRNA, such as RT-qPCR and microarray analysis, can also contribute to inconsistencies in results [24,27].

The point-of-care (POC) detection of cancer biomarkers provides an effective means for early-stage diagnosis. The cytokines, especially IL-6 and IL-8, have been used as potential biomarkers allowing the diagnosis of various benign oral lesions from malignant ones. Various electrochemical and optical biosensors have been developed to detect interleukins [28]. Studies on clinical units and mouse models helped to reveal many cytokines that have a high correlation with specific diseases, overlaying an efficient way to develop Biology Collector (BIOCO) in clinics to promote the research in cytokine development platforms [29]. Cytokines can play a key role in disease management and diagnosis as an immune mediator, similarly to pathophysiology-based sepsis, where pro- and anti-inflammatory cytokines have a double-edged function [30]. Recent studies have focused on using molecular testing to guide targeted treatments for CRC patients, but introducing novel molecular tests into routine clinical practices remains a huge challenge [31]. Interleukins, which can be detected in blood circulation even in the case of localized tumors, have the potential to serve as biomarkers for detecting cancers, predicting disease outcomes, and managing therapeutic choices [32]. The detection of specific cytokines in blood can cost-effectively and non-invasively assist in the detection of cancer, as well as in determining the appropriate therapy and monitoring the progression of the disease [31,32,33,34].

2. Molecular Pathways and Cytokine Role in CRC

3. Advancements in Cytokine Detection and Monitoring Clinically

4. Cytokines’ Role in CRC

4.1. Forkhead Box P3 (FOXP3)

4.2. Tumor Necrosis Factor-α (TNF-α)

4.3. Interferon-Gamma (IFN-γ)

5. Interleukins in Colorectal Cancer