Leukemia Therapy: Mechanisms of Drug Resistance and Investigational Strategies
Ami K. Patel
Boston University School of Medicine, Boston, MA 02118, USA.
Mei Zhang
Department of Molecular Pharmacology, Small Molecule Platform, EMD Serono Research Institute, Inc, Billerica, MA 01821, USA.
Xudong Huang *
Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
*Author to whom correspondence should be addressed.
Abstract
Certain types of leukemia are amongst the first neoplasias to be “cured” with relatively high 5-year remission rates. This is largely due to targeted therapeutics. However, considerable resistance to tumor-specific targeting drugs has developed due to the presence of abundant cancer stem cells, profound genetic diversity, redundant growth/survival pathways and residual disease. Although these issues propose a challenge, they also provide the opportunity for novel innovations of therapy which currently include the development of multi-target kinase inhibitors, multiple drugs acting on multiple targets, key upstream targets covering multiple downstream targets and the future direction of hybrid molecules targeting two or more targets in different pathways.
Keywords: Leukemia, targeted therapeutics, drug resistance, novel therapies, multi-target kinase inhibitors, hybrid molecules.