From Olga Pozdnyakova, Jeffery Kutok, and Scott Rodig: Emerging Targeted Therapies for Lymphoid Malignancies

http://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2010-0391-RA

SPECIAL SECTION–PERSPECTIVES ON TARGETED THERAPIES FOR TREATMENT OF HUMAN CANCERS

Emerging Targeted Therapies for Lymphoid Malignancies

Olga Pozdnyakova, MD, PhD; Jeffery L. Kutok, MD, PhD; Scott J. Rodig, MD, PhD

Context.—Our understanding of molecular events in the pathogenesis of hematologic malignancies has evolved substantially. The research data gathered in the past 3 decades have led to the definition of neoplastic disorders based on specific genetic and molecular alterations, which is reflected in the current World Health Organization's classification of tumors of hematopoietic and lymphoid tissues. Moreover, there have been dramatic successes in the development and implementation of therapies that specifically target the proteins and signaling cascades affected by tumor-specific genetic alterations.

Objective.—To review the development of select, novel therapies for lymphoid malignancies.

Data Sources.—We examine examples from the recent literature in targeting 4 major regulatory pathways: tyrosine kinase activation, transcription factor activity, apoptotic signaling, and histone acetylation in both preclinical models and early-stage (stage 1 and 2) clinical trials.

Conclusion.—Given the successes of novel compounds that target signaling pathways critical to the growth and survival of lymphoid tumor cells, the routine clinical use of molecularly targeted therapies for the treatment of lymphoid malignancies is likely in the near future.