Abstract
Gallium is antiproliferative to many types of cancer, due primarily to its ability to act as a non-functional mimic of ferric iron (Fe3+). Because Fe3+ is needed for ribonucleotide reductase activity — and thus DNA synthesis — gallium can inhibit DNA production and cell division. Diagnostic gallium scans have shown that hepatocellular carcinoma (HCC) is commonly avid for gallium. Furthermore, in vitro studies have found that gallium nitrate, and particularly gallium maltolate (GaM), have dose-dependent antiproliferative activity against HCC cell lines. Rationale thus exists to use GaM, an orally active compound that has been well tolerated in Phase I clinical trials, to treat patients whose HCC is gallium-avid in a gallium scan. Because gallium absorbed from orally administered GaM is bound predominately to serum transferrin, which travels to all tissues in the body, GaM has the potential to treat even distant metastases. A patient with advanced HCC (20 x 10 cm primary tumor, ascites around liver and spleen, resistant to sorafenib (Nexavar®)), whose cancer was highly gallium-avid in a 67Ga-scan, was treated with oral gallium maltolate at 1500 mg/day q.d. After four weeks of treatment, the patient had a large reduction in pain, with greatly increased mobility and quality of life, and significantly lowered serum bilirubin and inflammation- related liver enzymes. At eight weeks, CT scans showed apparent necrosis of the tumor.
Keywords: Gallium, gallium maltolate, gallium scan, hepatocellular carcinoma, HCC, antiproliferative activity, GaM treatment, Contemporaneous CT images, metastatic prostate carcinoma, cancer-associated hypercalcemia, lymphomas, GALLIUM SCANNING, ANTICANCER MECHANISMS
Anti-Cancer Agents in Medicinal Chemistry
Title: Hepatocellular Carcinoma Detection by Gallium Scan and Subsequent Treatment by Gallium Maltolate: Rationale and Case Study
Volume: 11 Issue: 6
Author(s): Lawrence R. Bernstein, Jacobus J.M. van der Hoeven and Robbert O. Boer
Affiliation:
Keywords: Gallium, gallium maltolate, gallium scan, hepatocellular carcinoma, HCC, antiproliferative activity, GaM treatment, Contemporaneous CT images, metastatic prostate carcinoma, cancer-associated hypercalcemia, lymphomas, GALLIUM SCANNING, ANTICANCER MECHANISMS
Abstract: Gallium is antiproliferative to many types of cancer, due primarily to its ability to act as a non-functional mimic of ferric iron (Fe3+). Because Fe3+ is needed for ribonucleotide reductase activity — and thus DNA synthesis — gallium can inhibit DNA production and cell division. Diagnostic gallium scans have shown that hepatocellular carcinoma (HCC) is commonly avid for gallium. Furthermore, in vitro studies have found that gallium nitrate, and particularly gallium maltolate (GaM), have dose-dependent antiproliferative activity against HCC cell lines. Rationale thus exists to use GaM, an orally active compound that has been well tolerated in Phase I clinical trials, to treat patients whose HCC is gallium-avid in a gallium scan. Because gallium absorbed from orally administered GaM is bound predominately to serum transferrin, which travels to all tissues in the body, GaM has the potential to treat even distant metastases. A patient with advanced HCC (20 x 10 cm primary tumor, ascites around liver and spleen, resistant to sorafenib (Nexavar®)), whose cancer was highly gallium-avid in a 67Ga-scan, was treated with oral gallium maltolate at 1500 mg/day q.d. After four weeks of treatment, the patient had a large reduction in pain, with greatly increased mobility and quality of life, and significantly lowered serum bilirubin and inflammation- related liver enzymes. At eight weeks, CT scans showed apparent necrosis of the tumor.
Export Options
About this article
Cite this article as:
R. Bernstein Lawrence, J.M. van der Hoeven Jacobus and O. Boer Robbert, Hepatocellular Carcinoma Detection by Gallium Scan and Subsequent Treatment by Gallium Maltolate: Rationale and Case Study, Anti-Cancer Agents in Medicinal Chemistry 2011; 11 (6) . https://dx.doi.org/10.2174/187152011796011046
DOI https://dx.doi.org/10.2174/187152011796011046 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Targeting Ras-RAF-ERK and its Interactive Pathways as a Novel Therapy for Malignant Gliomas
Current Cancer Drug Targets Anti-cancer Peptides from Ras-P21 and P53 Proteins
Current Pharmaceutical Design Drug Resistance in Renal Tumors of Childhood
Current Pharmaceutical Biotechnology Reversing Agents for ATP-Binding Cassette (ABC) Transporters: Application in Modulating Multidrug Resistance (MDR)
Current Medicinal Chemistry - Anti-Cancer Agents When Ubiquitin Meets NF-κB: A Trove for Anti-cancer Drug Development
Current Pharmaceutical Design A Functional Scaffold in Marine Alkaloid: An Anticancer Moiety for Human
Current Medicinal Chemistry Primary Cardiac Tumors: A Retrospective Study
Current Respiratory Medicine Reviews Prevalence of HIV in Patients with Malignancy and of Malignancy in HIV Patients in a Tertiary Care Center from North India
Current HIV Research Effects of Highly Active Antiretroviral Therapy on HIV-1-Associated Oral Complications
Current HIV Research Potential Therapeutic Applications of miRNA-Based Technology in Hematological Malignancies
Current Pharmaceutical Design Therapeutic Transfer of DNA Encoding Adenoviral E1A
Recent Patents on Anti-Cancer Drug Discovery Effects of Compounds from Passiflora edulis Sims f. flavicarpa Juice on Blood Coagulation and on Proteolytic Enzymes
Protein & Peptide Letters Transition Metal-Based Prodrugs for Anticancer Drug Delivery
Current Medicinal Chemistry Targeted Liposomal Drug Delivery in Cancer
Current Pharmaceutical Design Molecular Pharmacology and Pharmacogenomics of Artemisinin and its Derivatives in Cancer Cells
Current Drug Targets Post-Docking Optimization and Analysis of Protein-Ligand Interactions of Estrogen Receptor Alpha using AMMOS Software
Current Computer-Aided Drug Design Advancements in the Understanding of Paclitaxel Metabolism in Tissue Culture
Current Pharmaceutical Biotechnology Editorial (Thematic Issue: Research and Regulation: Challenges of Nanoproducts)
Recent Patents on Nanomedicine Integrase Interactor 1 in Health and Disease
Current Protein & Peptide Science The Urokinase Plasminogen Activator System: A Target for Anti-Cancer Therapy
Current Cancer Drug Targets