Devan Aswathy R, Kumar Ayana R, Nair Bhagyalakshmi, Anto Nikhil Ponnoor, Muraleedharan Amitha, Mathew Bijo, Kim Hoon, Nath Lekshmi R
Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi 682041, Kerala, India.
The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O.B. 653, Beer Sheva 84105, Israel.
Pharmaceuticals (Basel). 2021 Jul 9;14(7):656. doi: 10.3390/ph14070656.
Hepatocellular carcinoma (HCC) has emerged as one of the most lethal cancers worldwide because of its high refractoriness and multi-drug resistance to existing chemotherapies, which leads to poor patient survival. Novel pharmacological strategies to tackle HCC are based on oral multi-kinase inhibitors like sorafenib; however, the clinical use of the drug is restricted due to the limited survival rate and significant side effects, suggesting the existence of a primary or/and acquired drug-resistance mechanism. Because of this hurdle, HCC patients are forced through incomplete therapy. Although multiple approaches have been employed in parallel to overcome multidrug resistance (MDR), the results are varying with insignificant outcomes. In the past decade, cancer immunotherapy has emerged as a breakthrough approach and has played a critical role in HCC treatment. The liver is the main immune organ of the lymphatic system. Researchers utilize immunotherapy because immune evasion is considered a major reason for rapid HCC progression. Moreover, the immune response can be augmented and sustained, thus preventing cancer relapse over the post-treatment period. In this review, we provide detailed insights into the immunotherapeutic approaches to combat MDR by focusing on HCC, together with challenges in clinical translation.
肝细胞癌(HCC)已成为全球最致命的癌症之一,因其对现有化疗具有高度难治性和多药耐药性,导致患者生存率低下。应对HCC的新型药理学策略基于索拉非尼等口服多激酶抑制剂;然而,由于生存率有限和显著的副作用,该药物的临床应用受到限制,这表明存在原发性或/和获得性耐药机制。由于这一障碍,HCC患者被迫接受不完整的治疗。尽管已并行采用多种方法来克服多药耐药性(MDR),但其结果各不相同,成效甚微。在过去十年中,癌症免疫疗法已成为一种突破性方法,并在HCC治疗中发挥了关键作用。肝脏是淋巴系统的主要免疫器官。研究人员采用免疫疗法,因为免疫逃逸被认为是HCC快速进展的主要原因。此外,免疫反应可以增强并持续,从而在治疗后时期预防癌症复发。在本综述中,我们通过聚焦HCC,详细阐述了对抗MDR的免疫治疗方法以及临床转化面临的挑战。