A research team led by scientists from the Beth Israel Deaconess Medical Center (BIDMC) have found that arsenic, in combination with the drug all-trans retinoic acid (ATRA), may have the potential to be used as a treatment for cancer. For more detailed information, you can read the source article here, at BIDMC’s website, or view the original publication in Nature Communications here.
The History of Arsenic
Arsenic is one of the oldest known drugs and has been used to treat many different conditions over time. Although arsenic is extremely toxic in high doses, in the 19th century arsenic was used as an anti-leukemic treatment. It was re-discovered as a cancer treatment in the 1970s, and, in 1995, therapeutic dosage levels of arsenic in the form of arsenic trioxide (ATO), combined with a second drug called ATRA, gained approval from the FDA for the treatment of acute promyelocytic leukaemia (APL). This new drug combination significantly improved the treatment of APL. However, the mechanisms by which these drugs work to treat cancer are not well understood.
The effects of arsenic alone on cancer are thought to be complex. While some epidemiological evidence suggests that arsenic may be linked to an increased risk of cancer, a study of people in Chile has linked high levels of inorganic arsenic in drinking water to reduced breast cancer mortality rates.
The Recent Study
A research team led by Dr Kun Ping Lu and Dr Xiao Zhen Zhou has explored the processes underlying the effectiveness of ATO and ATRA as a combination cancer treatment. The results of their research showed that ATO and ATRA work together to destroy an enzyme called Pin1. Pin1 plays an important role in regulating oncogenic (tumour development) signalling networks. The study cites previous research that suggests Pin1 is hyperactivated in the majority of cancers and is associated with poor prognoses, and that people who have genetic alterations that cause a lower level of Pin1 expression tend to also have a lower risk of multiple forms of cancer. Pin1 is therefore thought to play an important role in many cancers.
The research team discovered that ATO and ATRA work together to target Pin1. ATO was found to inhibit, degrade, and bind to Pin1, while ATRA increased cellular ATO uptake. The study authors write, “ATO and ATRA, at clinically safe doses, cooperatively ablate Pin1 to block numerous cancer-driving pathways.” This drug combination was also shown to get rid of cancer stem cells in both animal models and patient-derived tumour triple-negative breast cancer models. This form of breast cancer is often resistant to chemotherapy and can be difficult to treat with existing drugs.
Future Directions
The researchers say that their findings may have implications for the treatment of triple-negative breast cancer. The researchers also say that the findings may be relevant to other types of cancer, and in particular, those that are Pin1-positive.
