**1. Introduction**

Colon cancer (CC) is highly malignant and is considered the second cause of death worldwide. For 2018 new cases, 10% of the newly recorded cases were dead [1]. However, the overall CC survival rate is improving due to the rapid development of screening tools and improved treatment options. This raised the need to develop effective approaches for medical intervention [2]. Moreover, CC is classified into four stages: stages I, II, III, and IV (**Figure 1**). Stage I includes the cancer growth through the mucosa, invasion of the muscular, and development through the colon or rectum wall, which is not infused into nearby tissue or lymph nodes. For stage II, cancer has infused through the colon or rectum wall and grown into nearby structures. In stage III, the cancer of the colon has spread to four or more lymph nodes, which may be

#### **Figure 1.**

*Colon cancer stages, development, and survival rates [3].*

metastasized to adjacent organs. Finally, cancer has spread to one or more distant organs in stage IV and may be diffused to the peritoneum [4].

According to the American Cancer Society, surgery may be the sole therapy for stage 0–I colon cancer. In most situations, this is accomplished by removing the polyp or eliminating the cancerous region with a colonoscope. However, if the malignancy is too big to be treated with local excision, a portion of the colon must be removed (partial colectomy) [5].

In stage I–II CC, on the other hand, surgery is a viable option for removing malignant tissue and adjacent lymph nodes, and it may be the only treatment required. Adjuvant chemotherapy is also suggested after surgery if the malignancy is at high risk of recurrence. 5-Fluorouracil with leucovorin, oxaliplatin, and capecitabine are the most common chemotherapeutic treatments. However, additional combinations may be employed. The typical treatment for stage II–III is a partial colectomy to remove the area of the colon with cancer as well as adjacent lymph nodes, followed by adjuvant chemotherapy. The FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin), and CapeOx (capecitabine and oxaliplatin) regimens are the most often utilized adjuvant chemotherapy regimens. However, depending on their age and medical conditions, some people may be able to receive 5-Flourouracil in combination with leucovorin or capecitabine alone [6].

In stage IV, CC most commonly spreads to the liver, but it can also extend to the lungs, brain, peritoneum (the lining of the abdominal cavity), or distant lymph nodes. Surgery is usually unlikely to cure certain tumors. This will entail surgery to remove the piece of the colon harboring cancer, adjacent lymph nodes, and any regions of cancer metastasis. Following that, chemotherapy is usually administered. If the malignancy has progressed to the liver, hepatic artery infusion may be utilized in some circumstances. If the metastasis cannot be eliminated because the tumorous tissues are too big or numerous, chemotherapy may be administered prior to surgery (neoadjuvant). If the tumors diminish, surgery to remove them may be attempted. Chemotherapy may be administered again following surgery. Ablation and embolization are two alternative options for destroying liver tumors. Furthermore, chemotherapy is the primary treatment if the disease has gone too far for surgery to be effective [7].

*DOI: http://dx.doi.org/10.5772/intechopen.105982 Colorectal Cancer Stages, Progress, Genetic Predisposition, and Immune Surveillance*

To manage the malignancy, most stage IV patients will get chemotherapy and/ or targeted treatments such as FOLFOX (leucovorin, 5-fluorouracil, and oxaliplatin "Eloxatin"), FOLFIRI (leucovorin, 5-fluorouracil, and irinotecan "Camptosar"), CAPEOX or CAPOX (capecitabine (Xeloda) and oxaliplatin), and FOLFOXIRI (leucovorin, 5-fluorouracil (leucovorin, 5-Fluorouracil, oxaliplatin, and irinotecan) [8].

Targeting medicines can be coupled with the regimens listed earlier. Bevacizumab (Avastin), ziv-aflibercept (Zaltrap), and ramucirumab (Cyramza) are drugs that target vascular endothelial growth factor (VEGF). On the other hand, cetuximab (Erbitux) and panitumumab (Vectibix) are drugs that target EGFR. 5-Fluorouracil and leucovorin with a targeted medication, capecitabine with a targeted drug, irinotecan with a targeted drug, cetuximab alone, and panitumumab alone are examples of the targeted regimens combinations with the chemotherapy. Several variables influence regimen selection, including past treatments [6].

After all, CC genetic predisposition and the host's immune responses influencing cancer growth were discussed and illustrated to understand the best management approach depending on the CC stage and pathogenesis.

### **2. Genetic predisposition of colon cancer**

### **2.1 Genes involved in colon cancer expansion and prognosis**

The driver genes played vital regulatory roles in essential pathways for cellular division, cell survival, fate, and genome stability. For example, the RAS mitogenactivated protein kinase (MAPK) is essential for cellular division. Additionally, carcinogenesis is linked to the mutations, which are reported in the Kirsten rat sarcoma viral oncogene homolog gene (KRAS), Adenomatous Polyposis Coli gene (APC), Tumor Protein 53 gene (P53), and SMAD family member 4 genes, Mothers against decapentaplegic homolog 4 gene (SMAD4). Additionally, epigenetics in conjunction with intestinal dysbiosis, bacterial drivers, and persistent mucosal inflammation are all contributing factors to CC [9, 10].

On the other hand, KRAS, nuclear factor-κB gene (NF-κB), signal transducer and activator of the transcription-3 gene (STAT-3), B-cell lymphoma type-2 gene (BCL-2), BCL-2-associated protein X gene (BAX), and the transforming growth factor-β gene (TGF-β) were selected in the molecular testing for their correlation in the CC predisposition and progression [9–11].

### **2.2 Kirsten rat sarcoma viral oncogene (KRAS)**

Regarding CC, genes enrolled in cancer development are proto-oncogene (KRAS), tumor suppressor gene (P53 and APC), antiapoptotic gene (BCL-2), and proapoptotic gene (BAX) [10]. Mutations in the KRAS oncogene are common in human malignancies, notably those of the pancreas, gallbladder, bile duct, thyroid gland, and non-small cell lung cancer with CC. These mutations may influence prognosis and medication responsiveness to anticancer agents targeting the KRAS protein pathway [12].

KRAS mutations are considered an early influencer in CC that happened in 30 to 40% of patients. On the other hand, the KRAS gene activates NF-κB signaling in cancerous cells and triggers several proinflammatory mediators [9, 10, 12, 13].

The conventional first-line treatment for advanced CC is chemotherapy based on 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX). KRAS mutations, particularly G12D, are associated with a poor response to the conventional treatment and a significant risk of recurrence. Furthermore, KRAS mutations are strong indicators of EGFR inhibitor therapy success in individuals with CC. Monoclonal antibodies targeting EGFR have been shown to assist CC patients who had failed previous treatments. Cetuximab and panitumumab are EGFR-targeting drugs used to treat KRAS mutations. LUMAKRASTM (sotorasib), also known as AMG 510, recently received accelerated approval from the US Food and Drug Administration (FDA) for the treatment of adult patients with KRAS-G12C mutations who have received at least one prior systemic therapy [14, 15].
