Colorectal Cancer: Disease Process, Current Treatment Options, and Future Perspectives

Abstract

Colorectal cancer (CRC) is one of the deadliest malignancies in the US, ranking fourth after lung, prostate, and breast cancers, respectively, in general populations. It continues to be a menace, and the incidence has been projected to more than double by 2035, especially in underdeveloped countries. This review seeks to provide some insights into the disease progression, currently available treatment options and their challenges, and future perspectives. Searches were conducted in the PubMed search engine in the university’s online library. The keywords were “Colorectal Cancer” AND “disease process” OR “disease mechanisms” OR “Current Treatment” OR “Prospects”. Selection criteria were original articles published primarily during the period of 2013 through 2023. Abstracts, books and documents, and reviews/systematic reviews were filtered out. Of over 490 thousand articles returned, only about 800 met preliminary selection criteria, 200 were reviewed in detail, but 191 met final selection criteria. Fifty-one other articles were used due to cross-referencing. Although recently considered a disease of lifestyle, CRC incidence appears to be rising in countries with low, low–medium, and medium social demographic indices. CRC can affect all parts of the colon and rectum but is more fatal with poor disease outcomes when it is right-sided. The disease progression usually takes between 7–10 years and can be asymptomatic, making early detection and diagnosis difficult. The CRC tumor microenvironment is made up of different types of cells interacting with each other to promote the growth and proliferation of the tumor cells. Significant advancement has been made in the treatment of colorectal cancer. Notable approaches include surgery, chemotherapy, radiation therapy, and cryotherapy. Chemotherapy, including 5-fluorouracil, irinotecan, oxaliplatin, and leucovorin, plays a significant role in the management of CRC that has been diagnosed at advanced stages. Two classes of monoclonal antibody therapies have been approved by the FDA for the treatment of colorectal cancer: the vascular endothelial growth factor (VEGF) inhibitor, e.g., bevacizumab (Avastin®), and the epidermal growth factor receptor (EGFR) inhibitor, e.g., cetuximab (Erbitux®) and panitumumab (Verbitix®). However, many significant problems are still being experienced with these treatments, mainly off-target effects, toxic side effects, and the associated therapeutic failures of small molecular drugs and the rapid loss of efficacy of mAb therapies. Other novel delivery strategies continue to be investigated, including ligand-based targeting of CRC cells.

The effective combination therapies with irinotecan for colorectal cancer

“…Panitumumab is an IgG2 monoclonal antibody that has a stronger affinity for EGFR than cetuximab, binds more readily to EGFR, and effectively blocks the binding of epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-α) ligands to EGFR ( Rastin et al, 2024 ) ( Figure 8 ). Panitumumab acts as a functional antagonist of EGF and TGF-α ligands, leading to the internalization and degradation of antibody-receptor complexes, thereby inhibiting the EGFR-mediated signaling pathway, and the signaling blockage leads to the inhibition of tumor cell division, which inhibits tumor growth, metastasis, and angiogenesis and promotes apoptosis of tumor cells ( Adebayo et al, 2023 ).…”

Current understandings of colibactin regulation

“…Colorectal cancer (CRC) is the third most commonly diagnosed and second deadliest form of cancer globally [ 1 ]. The incidence of CRC is increasing worldwide and is predicted to continue to do so into the future, particularly in economically-impoverished regions where access to screening programmes is limited [ 2 ]. Worryingly, there is a rising incidence rate of CRC in young adults, pointing to changes in risk factors during early life [ 1 ].…”

Caffeic acid phenethyl ester promotes oxaliplatin sensitization in colon cancer by inhibiting autophagy

“…Surgical intervention is a viable option for early-stage colon cancer, while advanced cases with distant metastasis necessitate systemic therapy such as chemotherapy, targeted therapy and immunotherapy 2 – 4 . Commonly used chemotherapeutic agents include oxaliplatin, 5-fluorouracil, irinotecan, and docetaxel 5 . With the increase in the use of targeted drugs and immunotherapy, more choices are available for the comprehensive treatment of colon cancer 6 .…”