DDW Editor Reece Armstrong covers news of a drug which could be used to treat triple-negative breast cancer with less side effects.
A less toxic treatment for a specific type of breast cancer may be on the horizon due to a new drug developed by a team at the University of Arizona.
The team from the University of Arizona have developed a drug that appears to stop cancer growth by targeting a specific gene integral to the disease’s advancement throughout the body.
The drug is targeting cancer growth in triple-negative breast cancer and whilst it has not yet been tested in humans, it was shown to eliminate tumours in mice. Importantly, what the researchers are looking to develop is a drug with non-toxic side effects, and testing in mice showed the compound had little to no effect on normal healthy cells. The researchers developed the drug to target a gene known as epidermal growth factor receptor (EGFR), which is an oncogene that in certain circumstances can transform a cell into a tumour cell.
The compound the researchers developed blocks EGFR from going to a part of the cell that drives survival of the cancer. It works by shutting down the functioning of the EGFR protein that acts in cancer cells but not normal cells. Cancer therapies cause many unwanted side-effects due to not being directed towards the cancer cells. As such they end up attacking parts of other, healthy cells.
Speaking about the research Joyce Schroeder, who co-wrote the paper with lead author Benjamin Atwell, a postdoctoral student in the Department of Molecular and Cellular Biology, says: “EGFR has been known to be an oncogene for six decades, and there’s a lot of drugs out there trying to target it, but they all had limitations that didn’t make them workable as drugs for breast cancer.”
The compound comes after decades of research and two previous drug development attempts by the University of Arizona. The first two drug technologies that Joyce Schroeder and her team created worked to kill the cancer cells, but they had problems.
Schroeder heads the university’s Department of Molecular and Cellular Biology and leads the lab where the research for the paper was conducted.
The first attempt saw a therapy target what Schroeder calls an ‘unstructured’ part of the EGFR protein, and as a result, the compound couldn’t act consistently and reliably.
The second attempt resulted in a compound that was too generalised and hit a part of the protein that also drove normal activities in healthy cells, making the drug toxic. For the latest compound, the team knew they had to develop a therapy that would not impact a normal cell and that would remain active inside the body. This meant developing a compound that could enter a cancer cell and target the correct part of the proteins, specifically, the part of the proteins created by the EGFR gene to stop cancer from spreading.
With success coming on the team’s third attempt, Schroeder describes the result as a ‘Goldilocks effect’.
“When we tested the drug in animal models, we got this fabulous result where it actually didn’t just stop the tumours from growing, it caused them to regress and go away, and we’re seeing no toxic side effects,” she says. “We are so excited about this because it’s very tumour specific.”
“Targeting triple-negative breast cancer has been difficult because it doesn’t have one of these obvious things to target,” Schroeder says. “People have known for a long time that triple-negative breast cancer cells express EGFR, but when the known EGFR drugs were thrown at it, it didn’t respond.”
Triple-negative breast cancer accounts for about 10 to 15% of all breast cancers. Triple-negative refers to the fact that the cancer cells test negative for the three other types of breast cancer – those driven by too much oestrogen, too much progesterone or too much of a protein called HER2, according to the American Cancer Society. About half of all cases of the disease overexpress the EGFR oncogene, according to the National Institutes for Health.
The next step for the drug will be to advance it towards human trials.
DDW Volume 24 – Issue 1, Winter 2022/2023
