Development of Traditional Chinese Medicine in combination with EGFR Inhibitors against Cancer

Abstract

Epidermal growth factor receptor (EGFR) is one of the most important and therapeutically significant targets in most cancer treatments, and EGFR-targeted therapy is widely performed to treat various tumors, such as non-small cell lung cancer. Although EGFR-targeted therapy has fewer side effects than conventional chemotherapy, they have limited applications and are prone to drug resistance. Traditional Chinese medicine (TCM), are promising solutions to address these challenges because of their biological activities, such as inhibition of EGFR-related signaling pathways, reversal of drug resistance, and mitigation of side effects of targeted therapy. Moreover, TCM is characterized by multiple targets, few side effects and good therapeutic effect Here, we summarized several typical traditional Chinese medicine monomers derived from traditional Chinese medicine that can be used along with EGFR inhibitors, as well as herbal plants with potential for natural product development and TCM. We focused on their mechanisms of action underlying the reversal of drug resistance, enhancement of drug efficacy, and mitigation of side effects; we also assessed relevant clinical studies that are available. However, the potential adverse effects (e.g., drug-drug interactions, hepatotoxicity, and immune-related side effects) of TCMs along with EGFR inhibitors need to be further investigated. This article provided new perspectives on the use of TCMs in EGFR-targeted therapy and emphasized the importance of safety assessment in future studies.

Keywords: EGFR; EGFR monoclonal antibody; EGFR-TKI; cancer; traditional Chinese medicine; traditional Chinese medicine monomers.

Figure 1

Structural diagram of dimers formed by EGFR and EGF ligand binding.

Figure 2

Schematic representation depicting the epidermal growth factor receptor signal transduction pathway.

Figure 3

Schematic diagram of the molecular pathways related to EGFR-TKI resistance. EGFR kinase domain mutations and the upregulation or activation of other RTKs (such as AXL, MET, HER2 and IGF-1R which can cross the suppressed EGFR signaling pathway and activate downstream pathways) lead to resistance to EGFR-TKIs.