Predicting Response To Bet Inhibitor In Combination With Palbociclib / Sorafenib Using A Computational Model And Its Validation: A Beat Aml Project Study

Background: In AML, leukemic transformation causes clonal expansion of immature cells through de-regulated cell division cycles. CDK4/CDK6 regulates neoplastic progression, which might represent an effective strategy for treating AML. But current clinical data shows either limited efficacy or elusive results. Bromodomain and extra-terminal (BET) inhibitors interferes with transcriptional complexes and disrupting gene transcription of key oncogenes such as MYC. Also, there is need to explore usage of other receptor tyrosine kinase inhibitors. Therefore, a drug combination strategy should be explored to overcome limited clinical efficacy.