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Gallium in cancer treatment
Philippe Collery1, Bernhard Keppler, Claudie Madoulet
1Service de Cancérologie, Polyclinique Maymard, rue Marcel Paul, Bastia, France. bernard.desioze@univ-reims.fr
Abstract:
Gallium (Ga) is the second metal ion, after platinum, to be used in cancer treatment. Its activities are numerous and various. It modifies three-dimensional structure of DNA and inhibits its synthesis, modulates protein synthesis, inhibits the activity of a number of enzymes, such as ATPases, DNA polymerases, ribonucleotide reductase and tyrosine-specific protein phosphatase. Ga alters plasma membrane permeability and mitochondrial functions. Ga salts are taken up more efficiently and more specifically by tumour cells when orally administered. New compounds have been prepared: Ga maltolate, doxorubicin-Ga-transferrin conjugate and Tris(8-quinolinolato)Ga(III), which show interesting activities. Ga toxicity is well documented in vitro and in vivo in animals. In humans, the oral administration Ga is less toxic, and allows a chronic treatment, allowing an improvement of its bioavailability in tumours, by comparison with the parenteral use. The anticancer activity of Ga salts has been demonstrated but other effects have also been noted such as many bone effects that could be useful in bone metastatic patients. Its has also been shown that a long period of administration could induce tumour fibrosis. Ga is synergistic with other anticancer drugs. Although not as potent as platinum in vitro, the anticancer activity of Ga should not be ignored, but the schedule of administration still needs to be optimised and new compounds are now under clinical investigations.
Insights
Gallium (Ga) shows promise as an anticancer agent by disrupting DNA and protein synthesis. Oral administration of Ga offers improved tumor bioavailability and reduced toxicity, with potential benefits for bone metastases.
Area of Science:
- Oncology
- Medicinal Chemistry
- Biochemistry
Background:
- Gallium (Ga) is a metal ion investigated for cancer treatment, following platinum.
- Ga exhibits diverse anticancer activities, including DNA and protein synthesis inhibition.
- Ga affects cellular processes like enzyme activity, membrane permeability, and mitochondrial function.
Purpose of the Study:
- To review the anticancer activities and therapeutic potential of gallium (Ga).
- To explore novel gallium compounds and their administration routes.
- To assess gallium's toxicity, synergistic effects, and clinical relevance.
Main Methods:
- Literature review of gallium's biochemical mechanisms and pharmacological effects.
- Analysis of in vitro and in vivo studies on gallium's efficacy and toxicity.
- Examination of clinical investigations and novel gallium compound development.
Main Results:
- Gallium inhibits DNA/protein synthesis, modulates enzyme activity, and alters cellular functions.
- Oral Ga administration enhances tumor uptake and bioavailability with reduced toxicity compared to parenteral routes.
- New compounds like Ga maltolate and doxorubicin-Ga-transferrin conjugate show promise.
- Gallium demonstrates anticancer activity, bone effects beneficial for metastases, and potential for tumor fibrosis with chronic use.
- Synergistic effects with other anticancer drugs are observed.
Conclusions:
- Gallium (Ga) possesses significant anticancer properties and therapeutic potential, particularly via oral administration.
- Further optimization of administration schedules and development of new Ga compounds are crucial for clinical application.
- Gallium's unique effects on bone and potential synergy warrant continued investigation in cancer therapy.