Combination therapy in cancer: The potential of tetrandrine as a polytherapy for acute myeloid leukemia

Abstract

Acute Myeloid Leukemia (AML) is the most common form of leukemia diagnosed in adults with the lowest survival rates. It is a heterogeneous disease and incidence rates increase yearly, with the overall survival of AML patients remaining low. Emerging treatment strategies are key in improving the recovery rates of those diagnosed with AML due to not all patients responding to currently used intense chemotherapeutics. For the best treatment of AML patients possible, new treatments must be developed and treatment biomarkers identified.

Tetrandrine is a calcium channel blocker that is a potential treatment. It has demonstrated anti-proliferation, pro-autophagic and apoptotic, and multidrug resistance reversal effects on solid cancer varieties, thought to be potentiated by acquired genomic abnormalities, and it is hypothesised that it could be repurposed to act in a similar role in haematological cancers, namely AML. Although research into the effects of tetrandrine in AML is limited, the genomic abnormalities within subsets of the disease may reveal patients that would benefit from tetrandrine treatment.

This review aims to explore the potential mechanisms of tetrandrine treatment in AML, drawing on information gained through tetrandrine treatment in solid cancer. The main focus will be interactions with genes, protein, and pathways commonly dysregulated in AML, namely Tumour Protein 53 (TP53), C-Myc (MYC), Kirsten Rate Sarcoma Virus (KRAS), Vascular Endothelial Growth Factor (VEGF), Fms-like tyrosine kinase 3 (FLT3) and Nuclear Receptor Subfamily 4A1 (NR4A1) as well as the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3)-inflammasome and calcium–calmodulin (CaM)-dependent protein kinase II (CaMKII).