Recognition of our FTO inhibitor in the clinic.Role of...

Recognition of our FTO inhibitor in the clinic.

Role of N6-methyladenosine RNA modification in cancer
https://onlinelibrary.wiley.com/doi/full/10.1002/mco2.715

"CS1 (bisantrene) and CS2 (brequinar) have been identified as specific inhibitors of FTO, which can inhibit the self-renewal and immune evasion of cancer stem cells and exhibit potent antitumor effects in many types of cancer. They can significantly attenuate the self-renewal and reprogramming of leukemia stem/initiating cells by inhibiting the expression of immune checkpoint genes, especially LILRB4.402 CS1 and CS2 showed higher efficacy than FB23-2 at inhibiting AML cell viability. Among the FTO-targeted drugs, bisanthrene was the first inhibitor to enter clinical trials. In this phase II study, the clinical safety and efficacy of bisantrene were evaluated in an initial cohort of patients with relapsed/refractory AML.403 Of the 10 patients enrolled in the study, four showed a clinical response to bisantrene with acceptable cardiac toxicity. Given the observed low toxicity, a follow-up study is planned to combine bisantrene with a complementary antileukemia therapy. These findings suggest that bisantrene has a promising antileukemic activity and an acceptable safety profile. Small-molecule drugs targeting m6A regulators are gradually being developed and optimized. In the future, more of these drugs are expected to enter clinical research, either alone or in combination with chemotherapeutic agents or checkpoint inhibitors, to treat cancer. Thus, m6A can be leveraged in cancer immunotherapy through indirect RNA therapy, ICIs, cytokine therapy, and direct targeting of m6A regulators."