Introduction: Acute lymphoblastic leukemia (ALL) is a significant cause of cancer-related morbidity and mortality. Major advances in the understanding of the pathogenesis of ALL have uncovered new disease-associated biomarkers that can be targeted by biological and small-molecule therapeutics.
Areas covered: In this review, the authors examine novel approaches to target and drug discovery in ALL over the past 10 years. Cell surface antigens can be targeted by engineered mAbs and chimeric antigen receptor T cells. Detailed mechanistic studies in Philadelphia chromosome-positive ALL and ALL with mixed lineage leukemia rearrangements highlight current molecular approaches to target and drug discovery. Genomic technologies have uncovered genetic alterations that are potentially targetable. In addition, phenotypic screening can uncover unexpected targets. New targets in ALL include cell surface antigens, kinases, tumor suppressors, transcription factors, epigenetic regulators and metabolic enzymes.
Expert opinion: There are a number of effective approaches for discovering novel targets in ALL. Target validation is essential for further development of new therapeutics. Identifying select patient subsets with specific genetic vulnerabilities will be important in moving these therapeutics forward clinically.
Keywords: acute lymphoblastic leukemia; drug discovery; functional genomics; genetic alterations; mixed lineage leukemia; target discovery.