Reharnessing the therapeutic potential of gallium-based compounds in oncology: From the laboratory to the clinic. Pharmacol Rev 2026 Jul;78(4):100138
Date
06/17/2026Pubmed ID
42302450DOI
10.1016/j.pharmr.2026.100138Scopus ID
2-s2.0-105041812091 (requires institutional sign-in at Scopus site) 1 CitationAbstract
Despite advances in the treatment of certain malignancies, it is anticipated that there will be 626,140 cancer deaths in the United States in 2026. Thus, there remains a great need to develop new antineoplastic drugs with unique mechanisms of action distinct from those of existing drugs. Also relevant is revisiting agents that showed promise in early research. Some of these agents struggled to advance for reasons including an incomplete understanding of their molecular targets and insufficient commitment to pursuing their development. Gallium compounds initially gained attention as radiogallium 67Ga complexes for tumor imaging in cancer patients, but were later found in clinical trials of nonradioactive gallium nitrate to have antineoplastic activity against lymphoma and urothelial malignancies. Coincident with this, tris(8-quinolinolato)gallium(III) has been shown to be active against solid tumors and has now re-emerged in clinical trials as oral AP-002. Subsequent investigations showed that gallium exerts its antineoplastic activity by disrupting iron-dependent processes essential to cancer development and growth. Recent preclinical studies of oral gallium maltolate demonstrated its activity against glioblastoma, an aggressive brain tumor, leading to a Food and Drug Administration-approved phase 1 clinical trial for patients with relapsed glioblastoma. This review will focus on the evolution of gallium compounds in malignancy; advances in our knowledge of their mechanisms of action and tumor resistance; their interactions with cellular iron homeostasis and other targets; the past and present preclinical and clinical experience with gallium compounds; and the development of promising gallium-based agents on the horizon. SIGNIFICANCE STATEMENT: Gallium compounds showed anticancer activity in early clinical studies; however, an incomplete understanding of their mechanisms of action and resistance hindered the selection of patients most likely to benefit from treatment. Herein, we review the development of gallium compounds from early preclinical research to clinical trials for cancer. Recent insights into gallium's molecular targets have advanced the translation of gallium from the laboratory to a clinical trial of oral gallium maltolate in glioblastoma. Newer gallium compounds are being developed; their advancement is eagerly anticipated.
Author List
Chitambar CR, Zoss CJ, Al-Gizawiy MM, Schmainda KM, Connelly JMAuthors
Jennifer M. Connelly MD Professor in the Neurology department at Medical College of WisconsinKathleen M. Schmainda PhD Professor in the Biophysics department at Medical College of Wisconsin
