Repositioning Lidocaine as an Anticancer Drug: The Role Beyond Anesthesia

Abstract

While cancer treatment has improved dramatically, it has also encountered many critical challenges, such as disease recurrence, metastasis, and drug resistance, making new drugs with novel mechanisms an urgent clinical need. The term “drug repositioning,” also known as old drugs for new uses, has emerged as one practical strategy to develop new anticancer drugs. Anesthetics have been widely used in surgical procedures to reduce the excruciating pain. Lidocaine, one of the most-used local anesthetics in clinical settings, has been found to show multi-activities, including potential in cancer treatment. Growing evidence shows that lidocaine may not only work as a chemosensitizer that sensitizes other conventional chemotherapeutics to certain resistant cancer cells, but also could suppress cancer cells growth by single use at different doses or concentrations. Lidocaine could suppress cancer cell growth in vitro and in vivo via multiple mechanisms, such as regulating epigenetic changes and promoting pro-apoptosis pathways, as well as regulating ABC transporters, metastasis, and angiogenesis, etc., providing valuable information for its further application in cancer treatment and for new drug discovery. In addition, lidocaine is now under clinical trials to treat certain types of cancer. In the current review, we summarize the research and analyze the underlying mechanisms, and address key issues in this area.

Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis

“…Lidocaine is a local anesthetic used for relieving neuropathic pain, regional pain, and hyperalgesia in clinical therapy [ 6 ]. In recent years, lidocaine has been used as an anticancer drug in cancer treatment [ 7 ]. Sui et al reported that lidocaine inhibited cell metastasis in gastric cancer by upregulating miR-145 to activate the NF-κB signaling pathway [ 8 ], and Sun and Sun found that lidocaine retarded lung cancer progression by regulating the miR-539/EGFR axis [ 9 ].…”

Local anesthetics impair the growth and self-renewal of glioblastoma stem cells by inhibiting ZDHHC15-mediated GP130 palmitoylation

“…This will confirm the significance of anesthetics for cancer patients and guide clinical practice. Local anesthetics can reach the circulatory system via absorption from the injection site or direct intravenous injection (e.g., lidocaine) to affect the circulating tumor cells released from the primary tumor during surgery [38]. Amide local anesthetics act on nerve cells by blocking voltage-gated sodium channels, resulting in decreased depolarization and repolarization rates of excitatory nerve cell membranes [39,40].…”

Lidocaine liposome modified with folic acid suppresses the proliferation and motility of glioma cells via targeting the PI3K/AKT pathway

“…Lidocaine is widely used as a local anesthetic. In addition to having anesthetic effects, lidocaine has also been reported to have inhibitory effects on tumors (25)(26)(27). A previous study demonstrated that lidocaine can inhibit vascular endothelial growth factor-A-induced angiogenesis, and therefore may be able to suppress cancer progression (28).…”