Unraveling the Complex Interconnection between Specific Inflammatory Signaling Pathways and Mechanisms Involved in HIV-Associated Colorectal Oncogenesis

SIMPLE SUMMARY: Despite the reduced death rate that comes with improved HIV treatment, chances of developing cancers in HIV infected individuals remains high. The main culprit here is exaggerated inflammatory responses, referred to as chronic inflammation. Inflammation happens when the tissue is damaged by an outside (e.g., injury by falling) or internal (e.g., infection by bacteria/parasites/viruses) sources. Normally, inflammatory responses assist with fighting off infections and promoting wound healing. Opportunistic infections are common in HIV and constantly trigger chronic inflammation responses and ultimately cancer development. Cancers are dubbed the wound that does not heal because cancers survive better in a chronic inflammatory state. Several inflammatory pathways are known to promote colorectal cancer initiation. These can be common in both colorectal cancers and HIV. Toll like receptor inflammatory pathways are important in the detection of injuries. Their role and therapeutic endeavors in HIV and cancers are well studied. These pathways connect to specific inflammatory pathways which in return interconnects with several other pathways that are involved in HIV-related colorectal cancers. Their contribution in colorectal cancers is impactful hence the suggestion to target specific or best, interconnected inflammatory pathways with the hope of halting cancer initiation, development and progression. ABSTRACT: The advancement of HIV treatment has led to increased life expectancy. However, people living with HIV (PLWH) are at a higher risk of developing colorectal cancers. Chronic inflammation has a key role in oncogenesis, affecting the initiation, promotion, transformation, and advancement of the disease. PLWH are prone to opportunistic infections that trigger inflammation. It has been documented that 15–20% of cancers are triggered by infections, and this percentage is expected to be increased in HIV co-infections. The incidence of parasitic infections such as helminths, with Ascariasis being the most common, is higher in HIV-infected individuals. Cancer cells and opportunistic infections drive a cascade of inflammatory responses which assist in evading immune surveillance, making them survive longer in the affected individuals. Their survival leads to a chronic inflammatory state which further increases the probability of oncogenesis. This review discusses the key inflammatory signaling pathways involved in disease pathogenesis in HIV-positive patients with colorectal cancers. The possibility of the involvement of co-infections in the advancement of the disease, along with highlights on signaling mechanisms that can potentially be utilized as therapeutic strategies to prevent oncogenesis or halt cancer progression, are addressed.