Meeting Summary

The first SOTS meeting on the leukemias brought together experts in AML to discuss molecular targeting, immunotherapy, antibody-delivered therapy, therapeutic resistance, and challenges to study design. Molecular discussions emphasized the multi-step, multi-mutation pathogenesis of AML and its implications for new agent development. Speakers urged a holistic approach to looking at mutant AML signal transduction and apoptotic pathways, and warned of the probable failure of "hyper"-targeted therapies in the face of mutant pathway redundancy and complexity. An array of signal transduction and apoptotic mediators were reviewed. The immunotherapy presentation highlighted opportunities for T-cell manipulation, and talks on multiple drug resistance elucidated the role of transport membrane transporter P-glycoprotein and its predictive value for induction outcome. Experts in antibody-delivered therapy discussed the role of antibody drug and toxin conjugates as promising therapeutics, as well as the importance of radiolabeling. Several challenges to effective study design were also brought forth by the discussions, including how to prioritize agents and patient groups for clinical trials; the dilemma of determining endpoints for therapy trials before biological targets are fully characterized within their larger metabolic context; and the persistent insufficiency of initial dosages in phase I trials. Selection and statistical strategies were offered to ease both results analysis and sample size requirements.