Treatment-Resistant Breast Cancer May Have Met Its Match with First-In-Class Drugs

The new compounds may lead to a highly effective, next-line treatment for estrogen receptor-positive breast cancer.

First-in-class drugs may offer a unique treatment approach for patients with breast cancer who have become resistant to standard therapies, according to a study published in eLife.

Approximately 80% of breast cancers are found to be estrogen-sensitive. Although they can often be treated effectively with hormone therapy, as many as one-third of these cancers eventually build up a resistance.

The novel compound estrogen receptor co-regulator binding modulators (ERXs) could potentially serve as a highly effective, next-line treatment for patients, according to the authors.

“This is a fundamentally different, new class of agents for estrogen receptor-positive breast cancer,” said author Dr Ganesh Raj. “Its unique mechanism of action overcomes the limitations of current therapies.”

The commonly used cancer drug tamoxifen is designed to attach to the estrogen receptor in cancer cells to prevent estrogen from binding to the receptor; however, the receptor can mutate and change its shape over time to prevent the treatment from successfully doing its job, according to the authors. As a result, the cancer cells begin multiplying.

“There has been intense interest in developing drugs that block the ability of the estrogen receptor—–the prime target in most breast cancers—–from interacting with the co-regulatory proteins that cause a tumor’s growth,” said Dr David Mangelsdorf, professor and chairman of the department of pharmacology.

Dr Mangelsdorf continued that blocking such protein-protein interactions “has been a dream of cancer researchers for decades.”

“Dr Raj and his colleagues have done the remarkable by discovering what could be the first-in-class of a therapeutic that realizes this dream,” Dr Mangelsdorf added.

The drug is designed to block co-factor proteins that need to attach to the estrogen receptor for cancer cells to multiply. The new molecule ERX-11 mimics a protein building block, according to the authors. Thus far, ERX-11 has been tested in mice and cancer cells derived from patients, and has been successful in both models. Furthermore, the investigators have observed no signs of toxicity in the tests.

“This could be a first-line breast cancer therapy down the line,” Dr Raj said. “It could even lead to new treatments for other hormone-sensitive cancers. For now, it offers hope for women with estrogen-sensitive breast cancer for whom conventional therapies fail.”

Another plus of the treatment if it successfully translates to humans is that ERX-11 could be taken orally, rather than as an infusion.