Allosteric Inhibition of ABL Kinases: Therapeutic Potential in Cancer

• Published in: Molecular cancer therapeutics Vol. 19; no. 9; pp. 1763 - 1769
• Main Authors: Jones, Jill K, Thompson, Eric M
• Format: Journal Article
• Language: English
• Published: United States 01.09.2020
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1535-7163.mct-20-0069

Tyrosine kinase inhibitors have revolutionized the world of cancer treatment in recent years, profoundly improving survival of patients with chronic myeloid leukemia (CML) and beyond. However, off-target toxicities of these inhibitors are well-described, and resistance has become a paramount concern. Novel allosteric inhibitors of the Abelson (ABL) family of tyrosine kinases, including GNF-2, GNF-5, and ABL-001, are equipped to overcome these issues. Several contemporary studies have demonstrated their potential efficacy in three key areas: primary hematologic and solid malignancies, metastasis, and combination with other small molecules. Further, ongoing clinical trials are investigating the efficacy of ABL-001 for the treatment of CML and recurrent solid tumors. This work reviews the current literature of the preclinical testing of GNF-2 and GNF-5 and the preclinical and clinical testing of ABL-001. Future research will continue to evaluate these promising inhibitors as both first-line therapy for solid tumors and salvage therapy when more traditional drugs such as imatinib fail.