CircRNAs as New Therapeutic Entities and Tools for Target Identification in Acute Myeloid Leukemia

Abstract

Acute myeloid leukemia (AML) is a genetically extremely heterogeneous disease. Drug resistance after induction therapy is a very frequent event resulting in poor medium survival times. Therefore, the identification of new targets and treatment modalities is a medical high priority issue. We addressed our attention to circular RNAs (circRNAs), which can act as oncogenes or tumor suppressors in AML. We searched the literature (PubMed) and identified eight up-regulated and two down-regulated circ-RNAs with activity in preclinical in vivo models. In addition, we identified twenty-two up-regulated and four down-regulated circRNAs with activity in preclinical in vitro systems, but pending in vivo activity. Up-regulated RNAs are potential targets for si-or shRNA-based approaches, and down-regulated circRNAs can be reconstituted by replacement therapy to achieve a therapeutic benefit in preclinical systems. The up-regulated targets can be tackled with small molecules, antibody-based entities, or other modes of intervention. For down-regulated targets, up-regulators must be identified. The ranking of the identified circRNAs with respect to therapy of AML will depend on further target validation experiments.

circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC)

“…EGFR-independent factors like histological changes, alternative pathways (c-Met, HER2 amplification, Activation of IGF1R), NRAS/KRAS mutations, and oncogenic fusion genes (RET, ALK, BRAF) also contribute [ 11 ]. Still, around 40-50% of resistance mechanisms remain unclear [ 12 ]. Understanding Osimertinib resistance is crucial for improving treatment and patient outcomes.…”