Regalado Cynthia Rosa, Balogh Mihály
Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, Netherlands.
Front Mol Biosci. 2024 Nov 27;11:1451611. doi: 10.3389/fmolb.2024.1451611. eCollection 2024.
As chemotherapy is still a cornerstone of colorectal cancer (CRC) treatment, chemotherapy-induced peripheral neuropathy (CIPN) presents significant clinical challenges, affecting millions worldwide. A subset of colon cancer patients (approximately 30%) develop chronic CIPN, with detrimental, untreatable neuropathic pain symptoms. The risk factors of such intractable chronic CIPN are unknown. However, there is growing literature data investigating the intriguing interplay of neurons and cancer (cancer neuroscience). Recent data shows that this interplay might have a key role in the development and severity of CIPN. Given its vast (patho)physiological roles in both colon cancer and neuropathy, MMP9 seems to be a key factor that might drive the development of neuronal damage in colon cancer patients. This review investigates the role of matrix metalloproteinase 9 (MMP9) in linking CRC to neuropathy, aiming to uncover shared mechanisms that could offer new therapeutic targets. By synthesizing insights from a broad range of studies published over the last 20 years, we explore MMP9's involvement in CRC progression, its role in CIPN, and the interconnected pathways influencing both conditions. These studies reveal MMP9 as a pivotal mediator in ECM remodeling, inflammation, and signal transduction pathways, emphasizing its modulation by macrophages. These shared mechanisms of colon cancer and CIPN pathophysiology suggest MMP9's potential contribution to neuropathic conditions in CRC patients, positioning it as a critical factor in disease progression and a promising therapeutic target. Future research should focus on longitudinal studies to assess MMP9's impact on neuropathy outcomes in CRC patients, exploring MMP9 inhibitors, and developing targeted interventions to mitigate the detrimental symptoms of CIPN. MMP9 also seems to be a feasible driving factor in the development of chronic CIPN in colon cancer patients.
由于化疗仍是结直肠癌（CRC）治疗的基石，化疗引起的周围神经病变（CIPN）带来了重大的临床挑战，影响着全球数百万人。一部分结肠癌患者（约30%）会发展为慢性CIPN，伴有有害的、无法治疗的神经性疼痛症状。这种难治性慢性CIPN的风险因素尚不清楚。然而，越来越多的文献数据正在研究神经元与癌症之间有趣的相互作用（癌症神经科学）。最近的数据表明，这种相互作用可能在CIPN的发生和严重程度中起关键作用。鉴于基质金属蛋白酶9（MMP9）在结肠癌和神经病变中都具有广泛的（病理）生理作用，它似乎是可能推动结肠癌患者神经元损伤发展的关键因素。本综述研究了基质金属蛋白酶9（MMP9）在将CRC与神经病变联系起来方面的作用，旨在揭示可能提供新治疗靶点的共同机制。通过综合过去20年发表的广泛研究的见解，我们探讨了MMP9在CRC进展中的作用、其在CIPN中的作用以及影响这两种情况的相互关联途径。这些研究表明MMP9是细胞外基质重塑、炎症和信号转导途径中的关键介质，强调了巨噬细胞对其的调节作用。结肠癌和CIPN病理生理学的这些共同机制表明MMP9对CRC患者神经病变状况的潜在影响，使其成为疾病进展中的关键因素和有前景的治疗靶点。未来的研究应侧重于纵向研究，以评估MMP9对CRC患者神经病变结局的影响，探索MMP9抑制剂，并开发有针对性的干预措施以减轻CIPN的有害症状。MMP9似乎也是结肠癌患者慢性CIPN发展中的一个可行驱动因素。
