Interesting new study released earlier this month:
This study explores the role of certain small particles called exosomes, which are released from bone marrow stem cells, in the progression and drug resistance of AML. The researchers found that these exosomes carry the specific protein FTO that can influence the behavior of cancer cells, making them more aggressive and resistant to chemotherapy. The exosomes work by altering a particular type of RNA molecule (LncRNA GLCC1) in a way that enhances its stability and activity. This RNA molecule then interacts with other proteins to activate a signaling pathway that promotes cancer cell growth and resistance to treatment. The study also showed that by blocking the activity of this RNA molecule, the aggressive behavior and drug resistance of the cancer cells could be reduced.
What I found fascinating about this work was the focus on FTO-exosomes and Ara-C-chemoresistance:
"Taken together, this study firstly evidenced the role and underlying mechanisms by which BM-MSCs-derived FTO-exo supported cancer aggressiveness and drug resistance in AML, and the main findings of this study were summarized as follows: (1) BM-MSCs-derived FTO-exo promoted cell proliferation, LSC properties and Ara-C-chemoresistance in AML."
For me, this highlights the pathway of synergy between the two drugs in the 1994 clinical trial in heavily pretreated relapsed and refractory children where they achieved an impressive 46% ORR (efficacy was observed in both AML and ALL). It appears one of the main roles of Zantrene may be to sensitize cancer cells through FTO Inhibition (and maybe other epitranscriptomic inhibitors function in the same way, provided chemoresistance is a driving factor for aberrant expression). It's like switching the 'on' switch back on when it has been turned off.
https://pubmed.ncbi.nlm.nih.gov/38048862/
