Implications of Breast Cancer Chemotherapy-Induced Inflammation on the Gut, Liver, and Central Nervous System

Abstract

Breast Cancer is still one of the most common cancers today; however, with advancements in diagnostic and treatment methods, the mortality and survivorship of patients continues to decrease and increase, respectively. Commonly used treatments today consist of drug combinations, such as doxorubicin and cyclophosphamide; docetaxel, doxorubicin, and cyclophosphamide; or doxorubicin, cyclophosphamide, and paclitaxel. Although these combinations are effective at destroying cancer cells, there is still much to be understood about the effects that chemotherapy can have on normal organ systems such as the nervous system, gastrointestinal tract, and the liver. Patients can experience symptoms of cognitive impairments or “chemobrain”, such as difficulty in concentrating, memory recollection, and processing speed. They may also experience gastrointestinal (GI) distress symptoms such as diarrhea and vomiting, as well as hepatotoxicity and long term liver damage. Chemotherapy treatment has also been shown to induce peripheral neuropathy resulting in numbing, pain, and tingling sensations in the extremities of patients. Interestingly, researchers have discovered that this array of symptoms that cancer patients experience are interconnected and mediated by the inflammatory response.

Toll-like receptor-mediated neuroinflammation: relevance for cognitive dysfunctions

“…Similar results were obtained with doxorubicin, another widely used chemotherapeutic [96]. Because compelling evidence suggests that the microbiota-gut-brain axis is also involved in CICI [97][98][99], it is important to investigate whether dysregulation of TLR signaling in enteric glia anticipates CNS neurodegeneration (see Outstanding questions).…”

Animal models of chemotherapy-induced cognitive decline in preclinical drug development

“…Peripheral inflammation and the subsequent release of different pro-inflammatory mediators (TNF-α, IL-1β, IL-6) resulting from hepatic injury led to neuroinflammation by different mechanisms. This causes structural and functional alterations in the hippocampus (Izadpanahi et al 2020;Brown et al 2021). Therefore, antiinflammatory therapies that focus on liver inflammation could evolve as therapeutic interventions in CICI.…”

Memantine Protects against Paclitaxel-Induced Cognitive Impairment through Modulation of Neurogenesis and Inflammation in Mice

“…Paclitaxel is an effective chemotherapeutic agent against various types of cancers. It has been demonstrated to induce CICI [33,34]. Some mechanisms have been reported [7,35], including endoplasmic reticulum stress and the paclitaxel-induced impairment of microtubule dynamics.…”