Overstimulated Steroid Receptor Coactivators May Be Viable Treatment Option for Cancer Patients

Compound kills breast, prostate, lung, and liver cancer cells without harming healthy cells.

Compound kills breast, prostate, lung, and liver cancer cells without harming healthy cells.

A drug candidate that overstimulates proteins critical to tumor growth shows promise as a new method of treating a wide range of cancers.

The demands of rapid cell division put a strain on cancer cells, therefore this new drug works by tipping cell stress over the edge. A study published in the August 10 issue of Cancer Cell showed that the drug candidate inhibits tumor growth in a mouse model of breast cancer and efficiently kills a broad range of human cancer cells.

“Our prototype drug works in multiple types of cancers and encourages us that this could be a more general addition to the cancer drug arsenal,” said study author David Lonard, PhD, of Baylor College of Medicine.

Cancer cells acquire mutation in oncogenes, which can transform healthy cells into cancer cells to support their growth and survival. Because of this, a great deal of research has focused on identifying oncogenes that could be targeted by cancer drugs. The steroid receptor coactivator (SRC) family of oncogenes are especially promising as therapeutic targets, as they are central to key signaling pathways that cancer cells use to rapidly grow, spread, and acquire drug resistance.

Cancer cells rely heavily on SRCs to orchestrate a wide range of cellular events, so, in theory, SRC stimulation might be just as effective as SRC inhibition at tipping the balance of signaling activity in cancer cells.

To test this theory, scientists screened hundreds of thousands of compounds to identify a potent SRC activator called MCB-613. This compound killed human breast, prostate, lung, and liver cancer cells while leaving healthy cells untouched. When administered to 13 mice with breast cancer, MCB-613 nearly completely eliminated tumor growth without causing toxicity. In the control group of 14 mice, tumors continued to grow by about threefold over a 7-week period.

The findings indicate that elevating SRC activity beyond the already high levels present in cancer cells further pressures its maximized stress response system and selectively kills them. Plans for future studies include the continuation of exploration of the mechanisms by which SRCs kill cancer cells and screening for even better SRC activators.

“We are optimistic that these drugs will eventually find their way into the clinic for use in patients,” said Bert O’Malley, MD, of Baylor College of Medicine.