Abstract
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.
Highlights
Liver cancer is a major health concern and a leading cause of cancer-related death worldwide with an annual incidence of over 850,000 new cases globally [1]
Flap endonuclease-1 (FEN-1) is a key enzyme involved in base excision repair (BER), which possesses gap endonuclease (GEN) activity, which is involved in the induction of apoptosis
The administration of 5-FU elevates Stearoyl-CoA desaturase (SCD) levels through the PI3K and JNK pathways in a time-dependent manner [101]. Another enzyme involved in lipid metabolism is carbonyl reductase 1 (CBR1), which protects the cells from lipid peroxidation
Summary
Liver cancer is a major health concern and a leading cause of cancer-related death worldwide with an annual incidence of over 850,000 new cases globally [1]. 70% of patients are diagnosed with disease recurrence within 5 years, and to date, no adjuvant therapies are available to forestall this complication [4]. Surgical procedures such as transarterial chemoembolization seem to be effective in the intermediate stage; such procedures are ineffective for advanced HCC stages. Several approaches have been deployed for years to sensitize resistant tumor cells by chemotherapy but with varying and limited positive results. In this context, the strong “immune-role” of tumor cells acquiring resistant phenotypes suggests that immunotherapeutic approaches can be novel strategies to target resistant tumor cells.
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