Scientists, including an Indian-American researcher, have identified a molecule that can help treat breast cancer, giving hope to patients who have become resistant to traditional therapies.
The first molecule in the class shuts off estrogen-sensitive breast cancer in a new way, the researchers said. First-class drugs are those that work by a single mechanism – in this case a molecule that targets a protein in the estrogen receptor of tumor cells.
The potential drug offers hope for patients whose breast cancer has become resistant to traditional therapies. “This is a fundamentally different class of agents for breast cancer with positive estrogen receptors,” said Ganesh Raj, a professor at the University of Texas Southwestern (UT Southwestern) Simmons Cancer Center. “Their unique mechanism of action overcomes the limitations of current therapies,” Raj said.
All breast cancers are tested to determine whether they require estrogen to grow and about 80% are found to be estrogen-sensitive, the researchers said. These cancers can often be treated effectively with hormone therapy, such as tamoxifen, but up to one-third of these cancers eventually become resistant, they said.
The new compound is a potentially very effective, next-line treatment for these patients, Raj said. Traditional hormonal drugs, such as tamoxifen, work by binding to a molecule called estrogen receptor in cancer cells, preventing estrogen from binding to the receptor, a necessary step for cancer cells to multiply.
However, the estrogen receptor may mutate and change its shape over time so that the treatment drug no longer fits perfectly with the recipient. When this happens, the cancer cells begin to multiply again. “There has been an intense interest in the development of drugs that block the ability of the estrogen receptor, the main target in most breast cancers, to interact with the co-regulatory proteins that cause tumor growth,” he said. David Mangelsdorf, UT Southwestern professor.
Blocking such “protein-protein interactions” has been a dream of cancer researchers for decades. The drug works by blocking other molecules – proteins called cofactors – that must also bind to the estrogen receptor in order for the cancer cells to multiply.
The new molecule, called ERX-11, mimics a peptide, or protein blocker. So far, it has been tested on mice and cancer cells extracted from patients and works well in both models, and there have been no signs of toxicity in the tests.
If it is successfully translated into human therapy, another advantage of ERX-11 is that it could be taken orally by patients rather than as an infusion. Researchers are hoping to get an ongoing clinical trial in about a year. The notion of protein-blocking cofactors has implications for the treatment of other cancers as well.
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