Progress in the discovery and development of small molecule methuosis inducers

Current cancer chemotherapies rely mainly on the induction of apoptosis of tumor cells, while drug resistance arising from conventional chemicals has always been a big challenge. In recent years, more and more new types of cell deaths including methuosis have been extensively investigated and recognized as potential alternative targets for future cancer treatment. Methuosis is usually caused by excessive accumulation of macropinosomes owing to ectopic activation of macropinocytosis, which can be triggered by external stimuli such as chemical agents. Increasing reports demonstrate that many small molecule compounds could specifically induce methuosis in tumor cells while showing little or no effect on normal cells. This finding raises the possibility of targeting tumor cell methuosis as an effective strategy for the prevention of cancer. Based on fast-growing studies lately, we herein provide a comprehensive overview on the overall research progress of small molecule methuosis inducers. Promisingly, previous efforts and experiences will facilitate the development of next-generation anticancer therapies.