The Potential Strategies for Overcoming Multidrug Resistance and Reducing Side Effects of Monomer Tubulin Inhibitors for Cancer Therapy.

Abstract

Tubulin is an essential target in tumor therapy, and this is attributed to its ability to target MT dynamics and interfere with critical cellular functions, including mitosis, cell signaling, and intracellular trafficking. Several tubulin inhibitors have been approved for clinical application. However, the shortcomings, such as drug resistance and toxic side effects, limit its clinical application. Compared with single-target drugs, multi-target drugs can effectively improve efficacy to reduce side effects and overcome the development of drug resistance. Tubulin protein degraders do not require high concentrations and can be recycled. After degradation, the protein needs to be resynthesized to regain function, which significantly delays the development of drug resistance. Using SciFinder® as a tool, the publications about tubulin-based dual-target inhibitors and tubulin degraders were surveyed with an exclusion of those published as patents. This study presents the research progress of tubulin-based dual-target inhibitors and tubulin degraders as antitumor agents to provide a reference for developing and applying more efficient drugs for cancer therapy. The multi-target inhibitors and protein degraders have shown a development prospect to overcome multidrug resistance and reduce side effects in the treatment of tumors. Currently, the design of dual-target inhibitors for tubulin needs to be further optimized, and it is worth further clarifying the detailed mechanism of protein degradation.