Asensi-Cantó Antonio, López-Abellán María Dolores, Castillo-Guardiola Verónica, Hurtado Ana María, Martínez-Penella Mónica, Luengo-Gil Ginés, Conesa-Zamora Pablo
Facultad de Ciencias de la Salud, Universidad Católica de Murcia (UCAM), 30107 Guadalupe, Spain.
Servicio de Farmacia Hospitalaria, Hospital Universitario Santa Lucía, 30202 Cartagena, Spain.
Cancers (Basel). 2022 Jul 1;14(13):3248. doi: 10.3390/cancers14133248.
Growing evidence shows that nerves play an active role in cancer development and progression by altering crucial molecular pathways and cell functions. Conversely, the use of neurotropic drugs, such as tricyclic antidepressants (TCAs), may modulate these molecular signals with a therapeutic purpose based on a direct antitumoral effect and beyond the TCA use to treat neuropathic pain in oncology patients. In this review, we discuss the TCAs' safety and their central effects against neuropathic pain in cancer, and the antitumoral effects of TCAs in in vitro and preclinical studies, as well as in the clinical setting. The current evidence points out that TCAs are safe and beneficial to treat neuropathic pain associated with cancer and chemotherapy, and they block different molecular pathways used by cancer cells from different locations for tumor growth and promotion. Likewise, ongoing clinical trials evaluating the antineoplastic effects of TCAs are discussed. TCAs are very biologically active compounds, and their repurposing as antitumoral drugs is a promising and straightforward approach to treat specific cancer subtypes and to further define their molecular targets, as well as an interesting starting point to design analogues with increased antitumoral activity.
越来越多的证据表明，神经通过改变关键的分子途径和细胞功能，在癌症的发生和发展中发挥着积极作用。相反，使用神经营养药物，如三环类抗抑郁药（TCA），可能基于直接的抗肿瘤作用以及超出TCA用于治疗肿瘤患者神经性疼痛的范畴，以治疗为目的调节这些分子信号。在本综述中，我们讨论了TCA的安全性及其对癌症神经性疼痛的中枢作用，以及TCA在体外和临床前研究以及临床环境中的抗肿瘤作用。目前的证据指出，TCA治疗与癌症和化疗相关的神经性疼痛是安全且有益的，并且它们阻断癌细胞从不同位置用于肿瘤生长和进展的不同分子途径。同样，也讨论了正在进行的评估TCA抗肿瘤作用的临床试验。TCA是具有很强生物活性的化合物，将其重新用作抗肿瘤药物是一种有前景且直接的方法，可用于治疗特定癌症亚型并进一步确定其分子靶点，也是设计具有增强抗肿瘤活性类似物的一个有趣起点。
