Abstract
Since arsenic trioxide was first approved as the front line therapy for acute promyelocytic leukemia 25 years ago, its anti-cancer properties for various malignancies have been under intense investigation. However, the clinical successes of arsenic trioxide in treating hematological cancers have not been translated to solid cancers. This is due to arsenic's rapid clearance by the body's immune system before reaching the tumor site. Several attempts have henceforth been made to increase its bioavailability toward solid cancers without increasing its dosage albeit without much success. This review summarizes the past and current utilization of arsenic trioxide in the medical field with primary focus on the implementation of nanotechnology for arsenic trioxide delivery to solid cancer cells. Different approaches that have been employed to increase arsenic's efficacy, specificity and bioavailability to solid cancer cells were evaluated and compared. The potential of combining different approaches or tailoring delivery vehicles to target specific types of solid cancers according to individual cancer characteristics and arsenic chemistry is proposed and discussed.
Highlights
Arsenic is a naturally occurring metalloid found as a trace element in the earth's crust[1]
Despite an increasing awareness of toxicity arising from arsenic compounds, arsenic trioxide (ATO) has established itself as an effective, broad spectrum anti-cancer drug
Following its successful establishment as the front line treatment for acute promyelocytic leukemia (APL) patients, researchers and clinicians have been working toward improving its effectiveness in treatment and reducing its side effects for solid cancers
Summary
Arsenic is a naturally occurring metalloid found as a trace element in the earth's crust[1]. Several attempts have been carried out to utilize arsenic's significant anti-cancer properties for treating solid tumors by increasing its bioavailability and specificity for carcinoma cells while reducing its administered dosage[9] These include sensitizing the cells prior to ATO treatment, employing it in combination therapy with other conventional chemotherapeutic agents to explore their synergistic actions or employing nanotechnology to increase bioavailability of ATO while reducing its systemic toxicity[10,11,12,13]. A group of physicians at Shanghai Second Medical University continued the study and remarkable results were observed from the clinical trial with patients of relapsed and refractory APL after very low doses of intravenous ATO were administered[15]. There is a crucial need for analyzing various possible approaches of increasing the bioavailability of ATO without raising its dosage
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