Promising drug for hormone therapy-resistant breast cancer enters human trials

A team of researchers at Chicago’s University of Illinois (UIC) have revealed that their promising drug which could prove an effective treatment for breast cancer patients who have proved unresponsive to hormone therapy has entered human trials.

TTC-352, as the therapy is known, is said to possess the effectiveness of similar treatments such as tamoxifen or aromatase inhibitors but with less harmful side-effects.

"Preclinical studies have shown that TTC-352, which is a selective oestrogen mimic, causes complete tumour regression, but unlike tamoxifen, may pose a reduced risk of uterine cancer development," explained Debra Tonetti, Associate Professor of Pharmacology and head of Biopharmaceutical Sciences in the UIC College of Pharmacy.

Greg Thatcher, Professor of Medicinal Chemistry and Pharmacognosy, added: "Its mechanism is different than that of tamoxifen and aromatase inhibitors, and it has been shown to work on cancers that have grown resistant to these standard-of-care drugs."

In the US, around one in eight women are affected by breast cancer, and around 80% of all cases of the disease are classified as oestrogen receptor-positive, meaning that the tumours can use the hormone to grow. To tackle this, doctors utilise a treatment known as hormone therapy, which blocks the body’s production of oestrogen or the tumour’s ability to feed off of it.   

"Hormone therapy is considered to be highly effective at fighting oestrogen receptor-positive breast cancer, but nearly half of all women who undergo this type of treatment still develop a resistance to the medication and experience a recurrence," Tonetti remarked.

The drug has progressed through lab and animal trials, and was authorised by the FDA in July last year to proceed to human studies. The team now hopes to investigate and determine the maximum tolerated oral dose in metastatic breast cancer patients whose disease has progressed despite endocrine therapy. The study will also investigate best response to treatment, duration of progression-free survival, duration of overall survival, overall safety profile, and the drug’s effect on tumour expression of the biomarker protein kinase C alpha.

"We have observed that breast cancers that develop a resistance to hormone therapy have elevated PKC alpha expression and our previous studies suggest that PKC alpha may predict a positive response to oestrogen mimics like TTC-352," Tonetti noted.

Should the trial demonstrate positive results, the team will be looking to bring TTC-352 to patients as a first-line treatment for oestrogen receptor-positive breast cancer that expresses PKC alpha.

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