One of the more critical aspects of oncology research has been the Colorectal cancer types. It is becoming more and more clear that RCC (right-sided colorectal cancer) and LCC (left-sided colon cancer) differ in tumor biology and spatiotemporal clinical presentation. These differences in mutation, prognosis, and treatment response, among other factors, have spurred research aimed at tailoring personalized treatments. This article aims to investigate the genomic, clinical, and treatment differences between right- and left-sided colorectal cancers.
Overview of Colorectal Cancer
Everywhere you go across the globe, CRC remains one of the leading causes of cancer-related death. To put things into perspective, the American Cancer Society (ACS) estimates that the United States will diagnose approximately 151,030 new cases in 2025. In addition to that estimate, ACS also estimates that there will be roughly 52,550 deaths reported in the US due to CRC by the same date, making it a two-way epidemic (American Cancer Society,2025). Colorectal cancers (CRCs) can be classified based on their location in the biome, specifically into right-sided and left-sided CRCs.
Colorectal cancer includes various types, each with unique characteristics. Tumor location uniquely shapes the cancer’s biology, including its molecular characteristics, clinical course, and treatment responsiveness. These cancers subdivide according to their localization: right colon (including the cecum, ascending colon, and part of the transverse colon) and left colon (the remainder of the transverse colon, descending colon, sigmoid colon, and rectum). Recognizing these differences is crucial for effectively customizing care and treatment.
Genomic Distinction Between Right-Sided And Left-Sided Colorectal Cancers
Right-Sided Colorectal Cancer (RCC)
Right-sided colorectal cancers (RCCs) exhibit distinct mutations in cellular genes and possess unique molecular characteristics. These tumors often exhibit various genomic alterations that decrease their effectiveness against standard treatment protocols. RCCs are more commonly associated with microsatellite instability (MSI) and mutations in mismatch repair (MMR) genes, which lead to impaired DNA repair system function.
1. Microsatellite Instability: Renal cell carcinomas (RCCs) frequently exhibit high levels of microsatellite instability (MSI-H) due to failures in DNA mismatch repair processes. Approximately 15% to 20% of all CRC cases have this characteristic, but it is much more prevalent among right-sided tumors. Researchers believe that MSI-H tumors carry an increased mutation load, which enhances their response to Immunotherapy by boosting tumor expression hypersensitivity to cytokine signaling.
2. KRAS and BRAF Mutations: Right-sided tumors, particularly those with MSI, often exhibit BRAF mutations. Additionally, RCCs exhibit fewer KRAS mutations than LCCs do. Both BRAF mutations and CIMP lead to a poor prognosis and resistance to treatment.
3. CpG Island Methylator Phenotype (CIMP): Hypermethylation that silences suppressor genes is something RCCs suffer from more frequently than LCCs do, which adds to their uniqueness among other subtypes.
Left-Sided Colorectal Cancer (LCC)
LCCs tend to display a more standard tumor mutational profile compared to right-sided tumors. In addition to KRAS, which regulates cell growth, apoptosis, and survival mechanisms, researchers identify other significant genes, including TP53 and PIK3CA.
1. KRAS Mutations: A thorough understanding of KRAS mutations enables the development of more effective strategies to manage disease progression and significantly improve patient outcomes. Although these mutations are often associated with worsened necrosis and resistance to EGFR inhibitors, some cases have shown enhanced therapeutic responses to agents like cetuximab or panitumumab.
2. TP53 Mutations: Tumor suppressor genes play a vital role in regulating cellular pathways that control cell division and ensure orderly cell growth and reproduction. When mutations occur in these genes, they can disrupt various steps within the genomic stability pathway. This disruption can lead to a breakdown of the cell cycle, resulting in uncontrolled production of excess cellular components.
3. PIK3CA mutations disrupt the PI3K/AKT signaling pathway in locally advanced cervical cancers (LCCs). This disruption promotes tumor growth and increases resistance to therapies that target specific pathways, rather than addressing the broader effects on cancerous cell clusters. As an alternative approach, surgeons can consider removing the clustered mass using non-invasive instruments.
Clinical Features and Outcomes
The differences between right and left-sided colorectal cancers dictate how they are diagnosed and treated and the outcomes associated with each form of cancer.
Right Sided Colorectal Cancer (RCC)
RCC tumors present at a more advanced stage than other types of RCC. Patients also report symptoms like anemia, fatigue, and loss of weight, which is due to bleeding or obstruction in the right colon. As with most RCC tumors, cecum and ascending colon tumors remain asymptomatic until significant obstructing bowel issues much later on in the disease progression.
Prognosis: Increased distant metastasis significantly reduces prognosis for those diagnosed with right-sided colorectal cancer.
On the other hand, patients with MSI-H or MMR deficiency mutations can use immunotherapies like pembrolizumab, which improves survival rates.
Left-Sided Colorectal Cancer
Symptoms for left colonic include but are not limited to rectal pain along with altered bowel habits, thus easier to detect. It leads to better outcomes overall.
Prognosis: Right-sided cancers have worse outcomes due to higher distant metastasis, so these usually will be diagnosed at a later stage, while left are less responsive to standard chemotherapy because these tend not gonna spread too far; hence, treatment becomes more effective
Treatment Considerations
The genetic differences between left and right-sided colorectal cancers affect treatment approaches.
1. Chemotherapy and Targeted Therapies: Patients with renal cell carcinomas (RCCs) that exhibit higher levels of microsatellite instability-high (MSI-H) markers, along with BRAF mutations, can be treated effectively with immune checkpoint therapies such as pembrolizumab and nivolumab. On the other hand, lung cancer cases (LCCs) with significant KRAS and PIK3CA mutations typically require conventional chemotherapy in combination with EGFR-targeted therapy, provided that the KRAS gene is wild-type.
2. Surgical Approach: Both left and right-sided colon cancers are amenable to surgical treatment, although the surgeries required for them will differ somewhat. While surgeons may perform complex procedures like right hemicolectomy for RCCs, they usually manage left-sided tumors with 3-segmental resection.
3. Immunotherapy: The introduction of Immunotherapy has significantly changed prescribing patterns for all individuals suffering from MSI-H cancers. Since RCCs have a higher frequency of MSI-H, these tumors do respond well to immune checkpoint inhibitors. However, this is not the case for LCCs, especially those with KRAS mutations, as they do not respond well to these treatments.
Conclusion
Colorectal cancers on the right and left sides exhibit differences in genomic profiling, clinical presentation, and their responses to treatment. Such disparities highlight the need for personalized medicine strategies. By deepening our understanding of the molecular biology of malignancies, we can design more tailored treatments and improve patient care by diagnosing therapeutically actionable traits, such as mutations or the overactivity of specific pathways. Further investigations are underway to develop more specific therapies and immunomodulatory treatment options for colorectal cancer.
The accurate assessment of the intestinal tumor region is essential for effectively managing colorectal cancer among practitioners. Guiding the initial diagnosis and shaping the subsequent management plan proves to be very helpful. Establish plans that prioritize patient outcomes without compromise.
Also Read-Home Nursing Services: Personalized Care in the Comfort of Your Home
