New Therapeutic Strategies in Acute Lymphocytic Leukemia

Abstract

Most drugs used in standard regimens for acute lymphoblastic leukemia (ALL) were developed more than 30 years ago. Since that time, several new drugs have been developed and incorporated into ALL treatment. In spite of this, novel therapeutic approaches are still needed to improve outcomes for high-risk or relapsed ALL. This manuscript discusses newer treatment strategies, including purine nucleoside analogs, monoclonal antibodies, antibody drug conjugates, mammalian target of rapamycin (mTOR) inhibitors, proteasome inhibitors, histone deacetylase (HDAC) inhibitors, hypomethylating agents, spleen tyrosine kinase inhibitors, Bruton's tyrosine kinase (BTK) inhibitors, Janus kinase-signal transducer and activator of transcription (JAK-STAT) inhibitors, anti-programmed cell death protein (anti-PD-1) antibodies, mitogen-activated protein kinase (MEK) inhibitors, CXCR4 antagonists, poly (ADP-ribose) polymerase (PARP) inhibitors, and FMS-like tyrosine kinase 3 (FLT3) inhibitors. Additionally, this manuscript discusses the impact of diagnostic approaches on management of ALL. Specifically, minimal residual disease is increasingly felt to be important and will likely dramatically impact the care of ALL patients in the near future.

New biomarkers and therapeutic strategies in acute lymphoblastic leukemias: Recent advances

“…Functionally relevant JAK/STAT genetic mutations and polymorphisms are significant for different categories of human diseases, especially in cancer and hematologic malignancies …”

First results of pilot protocol ALl-REZ-2016 for children with high risk groups of relapsed acute lymphoblastic leukemia

“…Общая выживаемость при рецидивах ОЛЛ зависит от многих факторов -времени наступления рецидива, выхода в ремиссию, уровня минимальной остаточной болезни (minimal residual disease -MRD), определяющей продолжительность ремиссии, токсичности проводимой терапии. Оптимизация режимов индукции ремиссии происходит по мере разработки новых моделей таргетной терапии [1].…”

Linking energy sensing to suppression of JAK-STAT signalling: A potential route for repurposing AMPK activators?

“…These observations suggest that, like the mTOR pathway, AMPK-mediated regulation of JAK-STAT signalling has also evolved such that multiple mechanisms and targets are used to limit its activation. Additional therapies are being developed with varying degrees of success [81,82].…”