New Drug Fortifies Efficacy of Common Cancer Drug

A combination of doxorubicin plus an aldose reductase inhibitor prevented cardiotoxicity in patients with colon cancer.

Investigators have discovered a new approach to increase the efficacy of a common cancer drug, while also reducing its cardiovascular toxicity, according to a study published by Scientific Reports.

Doxorubicin is a widely-used and effective cancer drug, but it can be toxic to the heart when administered in high doses. The authors of the study found that combining an inhibitor of the enzyme aldose reductase with doxorubicin can be an effective treatment for colon cancer.

The novel treatment approach was also found to reduce toxins that damage the heart, a serious side effect of doxorubicin, according to the study.

Previous studies have shown that exposure to carcinogens trigger oxidative stress, which drives cancer cell proliferation. Oxidative signals are also involved with growing new blood vessels for tumors. Reducing oxidative signals is the primary reason for using or consuming products that contain antioxidants to prevent cancer, according to the authors.

"We've shown that oxidative signals can be blocked by aldose reductase (AR) inhibitors," said lead author Satish Srivastava, PhD. "If we could prevent development of the new blood vessels in the cancer tissue driven by these signals, tumor growth and metastasis can be slowed down or prevented."

The investigators have been studying fidarestat, an AR inhibitor, to determine how it may prevent cancer growth and metastasis. In the United States, the drug has completed phase 2 clinical trials in preventing diabetic retinopathy, with no major adverse events discovered, according to the study.

Doxorubicin is prescribed to treat a range of cancers and is considered very cost-effective in relation to other cancer drugs; however, colon cancers have been observed to be particularly resistant to the drug and require a higher dosage for the treatment to be effective. Despite the necessity of a higher dosage to kill cancer cells, it can cause significant toxicity to the heart.

In the study, the authors examined human colon cancer cell lines in vitro and discovered that cancer cell growth was inhibited through a combination of the fidarestat and doxorubicin. Importantly, less doxorubicin was needed to be effective, according to the study.

The authors also found these results to be true in mouse models.

The investigators stated that the eventual goal is to use the combination therapy among patients with colon cancer in the hopes of reducing cardiotoxicity, according to the study.

"Since doxorubicin is one of the cheapest drugs that is effective against many types of cancer but rarely used in colon cancer, the combination therapy could be highly effective in combating colon cancer while drastically lowering risk of cardiotoxic side effects,” Dr Srivastava concluded.