Despite considerable progress in supportive care, life prolongation, and prevention of life-threatening complications, current therapeutic strategies suffer from the common neuralgic point of side effects and adverse events, often stemming from the promiscuity of therapeutic agents.
The long-lasting stagnation in overcoming this issue is most perceptible in anticancer therapies, which have failed to eliminate this phenomenon for decades. Given the global cancer burden of 18 million new cases annually, a progressive treatment solution addressing the promiscuity of therapeutics, such as ESiNAR-X®, may have an impact on millions of human lives.
Chronic myelogenous leukemia
CML is a clonal hematopoietic stem cell disorder characterized by an increase in myeloid lineage cells at all differentiation stages.
-driver of leukemogenesis
-encoding the BCR-ABL1 oncoprotein
Rapid progress in understanding the molecular basis of CML allowed for the development of tyrosine kinase inhibitors (TKI) which have revolutionized the management of CML, with the disease now having a five-year survival rate over 80%.
The evolution of these drugs to treat CML has been quite remarkable in a continuous fight against resistance. Nonetheless, despite the massive improvement in CML treatment over the last years, an important minority of patients (20–30%) display intrinsic or acquired resistance to treatment during the disease course.
The current strategies for addressing TKI resistance have mainly focused on improving the potency and specificity of the drugs and on overcoming the resistance driven by mutations in the BCR-ABL1 oncogene. Alternative approaches addressing current treatment challenges may be necessary for patients who fail to respond to TKIs and novel therapeutic modalities capable of targeting leukemic clones escaping TKI therapy could be game changers in the professional management of these patients.
inhibition of homologous off-targets
Recognizes exclusively the target RNA
does not interact with native off-targets
Poor cellular uptake
high doses needed to achieve the therapeutic effect
Exhibits spontaneous delivery to cells
more than 500 million molecules per cell
originating from chemistry and promiscuity
Shows no toxicity even at extreme concentrations
healthy cell viability more than 98%
only partial suppression of target RNA
Remarkable efficacy in target suppression
reduces BCR-ABL1 RNA levels in mice by 99% in 10 days
Non-selective therapeutic action
the cause of treatment side effects
Highly specific towards leukemic cells
reduces leukemic cell burden in mice by 50% in 10 days