Gould Harry J, Paul Dennis
Department of Neurology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Biomedicines. 2022 Apr 2;10(4):838. doi: 10.3390/biomedicines10040838.
The conventional treatment of cancer has been based on the delivery of non-selective toxins and/or ionizing energy that affect both the cancer and normal tissues in the hope of destroying the offending disease before killing the patient. Unfortunately, resistance often develops to these treatments and patients experience severe, dose-limiting adverse effects that reduce treatment efficacy and compromise quality of life. Recent advances in our knowledge of the biology of tumor cells and their microenvironment, the recognition of surface proteins that are unique to specific cancers and essential to cell growth and survival and signaling pathways associate with invasion and metastasis have led to the development of targeted therapies that are able to identify specific cellular markers and more selectively deliver lethal treatment to the invading cancer thus improving efficacy and limiting adverse effects. In the context of targeted approaches to cancer therapy, we present targeted osmotic lysis as a novel and fundamentally different approach for treating advanced-stage carcinoma that exploits the conserved relationship between voltage-gated sodium channels and Na, K-ATPase and has the potential to increase survival without compromising quality of life in a broad spectrum of highly malignant forms of cancer.
癌症的传统治疗方法一直基于使用非选择性毒素和/或电离能量,这些会同时影响癌症组织和正常组织,以期在杀死患者之前消灭致病疾病。不幸的是,这些治疗方法常常会产生耐药性,患者会经历严重的、剂量限制性不良反应,这降低了治疗效果并损害了生活质量。近年来,我们对肿瘤细胞及其微环境生物学的认识取得了进展,识别出特定癌症所特有的、对细胞生长、存活至关重要的表面蛋白,以及与侵袭和转移相关的信号通路,这促使了靶向治疗的发展,靶向治疗能够识别特定的细胞标志物,并更有选择性地将致死性治疗作用于侵袭性癌症,从而提高疗效并限制不良反应。在癌症治疗的靶向方法背景下,我们提出靶向渗透裂解作为一种治疗晚期癌症的全新且根本不同的方法,该方法利用电压门控钠通道与钠钾ATP酶之间的保守关系,有潜力在不影响广泛高度恶性癌症患者生活质量的情况下提高生存率。