Accelerating the Destruction of Messenger Molecules Could Improve Cancer Treatment

The small molecule drug, SI-2, found to improve cancer treatment in mouse models.

Rather than blocking messenger molecules that help cancer cells multiply and migrate, a new study published by Proceedings of the National Academy of Sciences suggests that accelerating the destruction of these cells could possibly improve cancer treatment.

"We studied a molecule called the steroid receptor coactivator 3 (SRC-3), which is also amplified in breast cancer 1 (AIB1). It plays an important role in breast cancer, but also in lung, ovary, prostate and pancreatic cancer," said Jin Wang, PhD, senior author of the study. "For years it's been known that eliminating SRC-3 from cancer cells results in the cells slowing down their proliferation and migration. We wanted to target SRC-3 because it regulates not one but many signaling pathways inside cancer cells."

A small molecule is needed to enter cancer cells easily and target SRC-3, according to the study.

Researchers developed a lab test in order to find molecules with the ability to target SRC-3. The researchers discovered and chemically modified SI-1 to increase its potency, which resulted in the creation of SI-2.

"We don't know exactly how SI-2 works. However, we know that it binds to SRC-3 and somehow triggers its degradation," Dr. Wang said in a press release. "We discovered that the more SI-2 we added to cancer cells, the less SRC-3 protein they had. In our experiments, cancer cells eventually died because they could not produce enough SRC-3 to maintain their growth."

Researchers also found that SI-2 stopped breast cancer tumor growth in a mouse model. Minimal toxicity to the heart was observed and there was no toxicity to the liver, spleen, kidney, lung and stomach, according to the study.

"SI-2 is the next step in a long effort to develop drugs against a key group of oncogenic drivers of many cancers, the SRC-family of coactivators,” said Dr. Bert W. O'Malley, MD, the other senior author of the study. “The paper reveals novel compounds with good efficacy against cancers and low toxicity for normal cells and animals,"

Researchers believe this study could help improve cancer treatment and hope it will create more cancer drugs that target other coactivators, the study concluded.