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After a protein which can treat triple-negative breast cancer; now a potential drug identified

By FnF Desk | PUBLISHED: 20, May 2018, 12:04 pm IST | UPDATED: 20, May 2018, 15:09 pm IST

After a protein which can treat triple-negative breast cancer; now a potential drug identified
New Delhi: 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-in-class molecule shuts down oestrogen-sensitive breast cancer in a new way, researchers said.
First-in-class drugs are those that work by a unique mechanism - in this case a molecule that targets a protein on the oestrogen receptor of tumour cells.
The potential drug offers hope for patients whose breast cancer has become resistant to traditional therapies.
"This is a fundamentally different, new class of agents for oestrogen-receptor-positive breast cancer," said Ganesh Raj, professor at the University of Texas Southwestern (UT Southwestern) Simmons Cancer Center.
"Its unique mechanism of action overcomes the limitations of current therapies," Raj said.
All breast cancers are tested to determine if they require oestrogen to grow and about 80 per cent are found to be oestrogen-sensitive, researchers said.
These cancers can often be effectively treated with hormone therapy, such as tamoxifen, but as many as a third of these cancers eventually become resistant, they said.
The new compound is a potential highly effective, next-line treatment for these patients, said Raj.
Traditional hormonal drugs, such as tamoxifen, work by attaching to a molecule called the oestrogen receptor in cancer cells, preventing oestrogen from binding to the receptor, a necessary step for cancer cells to multiply.
However, the oestrogen receptor can mutate and change its shape over time so that the treatment drug no longer fits neatly with the receptor. When this happens, the cancer cells start multiplying again.
"There has been intense interest in developing drugs that block the ability of the oestrogen receptor - the prime target in most breast cancers - from interacting with the co-regulator proteins that cause a tumour's growth," said David Mangelsdorf, professor at UT Southwestern.
"Blocking such "protein-protein interactions" has been a dream of cancer researchers for decades.
The drug works by blocking other molecules - proteins called co-factors - that also must attach to the oestrogen receptor for cancer cells to multiply.
The new molecule, dubbed ERX-11, mimics a peptide, or protein building block.
Earlier a findings, published in the journal Nature Communications, showed that by inhibiting a protein called TAK1, the researchers were able to reduce lung metastasis in mice with triple-negative breast cancer (TNBC).
TNBC is a deadliest type of breast cancer that comprises 20 per cent of breast cancer cases and is particularly difficult to treat.
"For this subtype of breast cancer, few treatment options are available to target metastasis, and typically, these treatments are associated with high toxicity," said co-author Min Yu, Assistant Professor from the University of Southern California.
"A better understanding of tumour cells and their interactions with organs and tissues could help us design targeted therapies specific for metastasis," Yu added.
According to the study, TAK1 enables malignant cells from the breast to survive in the lungs and form new metastatic tumours. 
Metastasis are the most common cause of cancer-related death.
There is already a potential drug, called OXO -- that can inhibit TAK1 -- and presumably make it much more difficult for breast cancer cells to form lung metastases. However, OXO is not stable in the blood, and therefore would not work in patients, the researcher said.
The researchers developed a nanoparticle -- consisting of a tiny fatty sac -- that works like a smart bomb to carry drugs through the bloodstream and deliver them directly to tumours.
The scientists loaded this nanoparticle with OXO, and used it to treat mice that had been injected with human breast cancer cells. While OXO did not shrink primary tumours in the breast, it greatly reduced metastatic tumours in the lungs with minimal toxic side effects.
"For patients with triple-negative breast cancer, systemic chemotherapies are largely ineffective and highly toxic. So nanoparticles are a promising approach for delivering more targeted treatments, such as OXO, to stop the deadly process of metastasis," Yu noted.