Where can biology of childhood ALL be attacked by new compounds?

Summary 

Although the majority of children with acute lymphoblastic leukemia (ALL) can be cured with combination chemotherapy, the challenge remains to salvage patients with resistant disease and to reduce treatment related toxicity. To meet this challenge, it will be essential to incorporate new agents targeting the biological Achilles Heels of this cancer more rapidly into currently available treatment regimen. Here we review the principles of current ALL therapy, recent advances in understanding ALL biology and discuss a selection of promising areas for drug development that may take advantage of the underlying leukemia biology. We focus particularly on strategies to interfere with common effector mechanisms that can be trigged by different individual oncogenic lesions and on new agents from drug development programs in adult oncology, as such agents will come with better chances for sustainable commercial development.

Keywords: Acute lymphoblastic leukemia, Targeted therapy, Autophagy, Apoptosis, MTOR inhibitors, AKT inhibitors, BH3-mimetics, Chemosensitization