Putting the brakes on aggressive breast cancer

Photograph of multi-colored glow sticks with a dark background. Photo by Lynda Olsen, CC BY 4.0 via Flickr.

In the United States, 1 out of every 8 women will be diagnosed with breast cancer in their lifetime(1). This is an overwhelming number, and complicated by the fact that breast cancer is one of the deadliest forms of cancer out there. It’s also one of the most common types of cancer in women. Doctors group breast cancer into multiple “subtypes” based on the presence or absence of three specific proteins. These proteins make breast cancer cells more vulnerable, because drugs can “target” these proteins to kill the cancer cells—kind of like how kryptonite weakens Superman. 

Unfortunately, triple-negative breast cancer (TNBC) doesn’t have any of these three proteins—hence the name “triple-negative.” Not having these proteins predisposes the cancer to being the most aggressive, even though it only accounts for about 15% of diagnosed breast cancer cases (1). In the clinic, aggressiveness in cancer translates to its ability to grow very fast, spread to other organs quickly, and become resistant to a lot of common chemotherapy drugs. Because of this, TNBC is like an evil Superman with no known kryptonite.

To defeat an evil Superman, we first need to understand how it behaves. In TNBC, this means understanding both how the kryptonite-less cells grow and how they spread to other organs. The latter is especially important because most patients don’t die because of their original tumor, but from the complications that result when it spreads to other parts of their body.

In recent years, scientists have been tracking the growth and movement of cancer cells by making them glow. It might sound like science fiction, but we have to get creative if we’re going to take down an evil Superman! To make this science fiction a reality, scientists genetically engineer human TNBC cells to make fluorescent proteins. These proteins help the TNBC cells emit light under a special type of microscope known as the fluorescent microscope. Then, they inject these cells into the mammary glands of mice, which mimics the natural environment of breast cancer in humans. Since only the injected, engineered human TNBC cells will glow, scientists can easily distinguish them from other cells. This allows them to better observe how they grow in the mammary gland and spread to other organs.

Scientists also use this technology to look for kryptonite candidates in TNBC. When scientists suspect that a protein may be a potential kryptonite, they engineer the glowing TNBC cells to stop making this protein. If the lack of this protein slows down the cancer’s growth and spread, they know that they have a promising new drug target.

There’s still a lot to do to find a treatment that works for TNBC patients, but glowing tumors have certainly been a part of the path forward.   

 


References

1.      Howlader N, et al. (eds). SEER Cancer Statistics Review, 1975–2017, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2017/, based on November 2019 SEER data submission, posted to the SEER web site, April 2020.


Kacey Rosenthal is a PhD candidate in the Department of Pharmacology at the University of Washington. She studies an aggressive form of breast cancer so that doctors can understand better how to stop it from growing and spreading.

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