A short paper has just appeared on PubMed
Affiliations include
City of Hope. Authors are Ying Qing,
Rui Su, and our own SAB member
Jianjun Chen
It's very brief but seems to give a history and summary of m6A research and FTO inhibition therapy:
...Based on these data, increased efforts have been made for the discovery of effective small-molecule FTO inhibitors...recently, Su et al. identified two highly efficacious small-molecule FTO inhibitors, i.e., CS1 (or Bisantrene) and CS2 (or Brequinar), which display potent in vitro and in vivo anti-tumor effects in both AML and solid tumors in which FTO is highly expressed...CS1 and CS2 treatments sensitize AML cells to T cell cytotoxicity by suppressing the expression of immune checkpoint gene LILRB4, supporting FTO inhibition as an effective strategy to overcome immune evasion induced by HMAs...Hence, potent small-molecule FTO inhibitors (represented by CS1 and CS2) hold great therapeutic potential, alone or in combination with other agents such as HMAs, for the treatment of refractory and relapsed cancer...
There's no reference to FTO inhibition synergising with anti PD-1 therapies (which from memory is what
@Mason14 was hopeful for) but it does highlight the synergies with HMAs (hypomethylating agents). This paper was quite brief and I can't see an immediate reason for it's publication other than to point out the HMA synergies - which were already known (
@RaceOncology any insight here?).
This article actually reminded me of
another paper of similar length that these three authors wrote. In November of 2019 a short article was published in
Blood (the journal not the liquid) which announced the discovery of the as yet unknown CS1 and CS2 molecules as potent FTO inhibitors. Eight months later our transformative 'COH Paper' was published using the discoveries outlined in the Nov-19 article. I'm sure I'm not alone in hoping that COH 2.0 is not eight months away - but this new article does suggest that COH are now focusing on the therapeutic synergies between FTO inhibition and hypomethylating agents.
(20min delay)