Rakshamani Tripathi1, Zulong Liu1, Rina Plattner1. 1. Department of Pharmacology and Nutritional Sciences, University of Kentucky School of Medicine, Lexington, Kentucky 40536.
Abstract
PURPOSE OF REVIEW: The goal of this review is to summarize our current knowledge regarding how ABL family kinases are activated in solid tumors and impact on solid tumor development/progression, with a focus on recent advances in the field. RECENT FINDINGS: Although ABL kinases are known drivers of human leukemia, emerging data also implicates the kinases in a large number of solid tumor types where they promote diverse processes such as proliferation, survival, cytoskeletal reorganization, cellular polarity, EMT (epithelial-mesenchymal-transition), metabolic reprogramming, migration, invasion and metastasis via unique signaling pathways. ABL1 and ABL2 appear to have overlapping but also unique roles in driving these processes. In some tumor types, the kinases may act to integrate pro- and anti-proliferative and -invasive signals, and also may serve as a switch during EMT/MET (mesenchymal-epithelial) transitions. CONCLUSIONS: Most data indicate that targeting ABL kinases may be effective for reducing tumor growth and preventing metastasis; however, ABL kinases also may have a tumor suppressive role in some tumor types and in some cellular contexts. Understanding the functions of ABL kinases in solid tumors is critical for developing successful clinical trials aimed at targeting ABL kinases for the treatment of solid tumors.
PURPOSE OF REVIEW: The goal of this review is to summarize our current knowledge regarding how ABL family kinases are activated in solid tumors and impact on solid tumor development/progression, with a focus on recent advances in the field. RECENT FINDINGS: Although ABL kinases are known drivers of human leukemia, emerging data also implicates the kinases in a large number of solid tumor types where they promote diverse processes such as proliferation, survival, cytoskeletal reorganization, cellular polarity, EMT (epithelial-mesenchymal-transition), metabolic reprogramming, migration, invasion and metastasis via unique signaling pathways. ABL1 and ABL2 appear to have overlapping but also unique roles in driving these processes. In some tumor types, the kinases may act to integrate pro- and anti-proliferative and -invasive signals, and also may serve as a switch during EMT/MET (mesenchymal-epithelial) transitions. CONCLUSIONS: Most data indicate that targeting ABL kinases may be effective for reducing tumor growth and preventing metastasis; however, ABL kinases also may have a tumor suppressive role in some tumor types and in some cellular contexts. Understanding the functions of ABL kinases in solid tumors is critical for developing successful clinical trials aimed at targeting ABL kinases for the treatment of solid tumors.
Authors: Rina Plattner; Brenda J Irvin; Shuling Guo; Kevin Blackburn; Andrius Kazlauskas; Robert T Abraham; John D York; Ann Marie Pendergast Journal: Nat Cell Biol Date: 2003-04 Impact factor: 28.824