Antibiotics and Cardiac Glycosides May Be Effective Cancer Treatments
Medications normally used to treat infections and heart conditions are promising cancer treatments, according to a recent study published in Cancer Research.1 These drugs were previously not known to have roles in modifying cellular epigenetics.
Epigenetic modifications can change gene expression and can be part of the cascade of genetic changes needed for cancer to develop. Researchers used colon cancer cell lines to perform an epigenetic screen of more than 1100 FDA-approved drugs to identify those that reactivated silenced gene expression.
"Human body cells have a natural defense, called tumor suppressor genes, which are silenced by epigenetic mechanisms triggered by cancer. We wanted to quickly find treatments that reverse this deregulation," explained lead author Noël Raynal, MSc, PhD, who is an investigator at the Sainte-Justine University Hospital Center Research Center in Quebec, Canada.
From the screen, the 14 most promising drugs were chosen. These drugs were antibiotics and cardiac glycosides with previously unknown epigenetic actions. Calcium signaling was shown as a novel pathway to target in re-activating tumor suppressor genes that had been previously silenced through epigenetic mechanisms.
"We identified a dozen or so drugs that reactivate tumor suppressor genes through an epigenetic mechanism that was never observed before," said Raynal.
"Epigenetic mechanisms control gene expression. They are highly deregulated in cancer cells. The mechanism that we discovered controls gene expression by targeting intracellular calcium levels."
Four drugs that epigenetically reprogram cancer cells are currently approved for cancer treatment. These 4 drugs act on histone modification and DNA methylation, not on epigenetic cancer signaling. As the 14 drugs identified in this study are already FDA-approved, they may become readily available for cancer treatment more quickly.
"Since these drugs' safety and efficacy in humans are already known and proven, they may readily go through clinical validation and be made available to patients more quickly," said Raynal.
"We need more research on drugs that target intracellular calcium signalling, such as cardiac glycosides and antibiotics. They hold huge potential for expanding the number of effective drugs to cure cancer patients."
1. Raynal NJ, Lee JT, Wang Y, et al. Targeting calcium signaling induces epigenetic reactivation of tumor suppressor genes in cancer [published online ahead of print December 30, 2015]. Cancer Res. doi:10.1158/0008-5472.CAN-14-2391.