New research shows potential for developing new targeted therapies for breast cancer that will not only stop cell growth in cancer cells, but also kill them without damaging healthy cells. Although targeted therapies are not new, this research identifies a new target, as well as a way to determine people who would benefit from future therapies aiming for that target.

Key Takeaways

  • People who undergo chemotherapy for breast cancer deal with side effects from their healthy cells being killed along with their cancer cells.Future cancer therapies could be targeted to make cancer treatments more effective and less damaging.Nearly 30,000 of the 325,000 people diagnosed with breast cancer every year carry a specific genetic variant that would make it possible to kill their cancer cells without harming their normal cells.Researchers are continuing to identify additional targets, which would expand the number of people who could benefit from targeted cancer therapies.

Like all cancers, breast cancer starts when normal, healthy cells undergo a change and start to divide so rapidly that the growth of the cells is uncontrolled. The result is a mass of cells, which is felt as a lump. After a diagnosis of breast cancer is made, treatment often may involve chemotherapy. But chemotherapy can be harsh, killing not only the bad cancer cells but also the good healthy cells and leaving people undergoing chemotherapy feeling very sick. In the future, there could be treatments that target only the cancer cells and preserve the healthy cells, making cancer treatment more effective and less harmful.

Results of collaborative research by scientists at Johns Hopkins University School of Medicine in Baltimore, Maryland, and Oxford University in Oxford, U.K., show that cancer cells can be targeted and then killed by disrupting an enzyme that is important for cell division. Their study was published in Nature on September 9. 

“Targeting cell division is a logical approach to killing cancer cells, since cancer is abnormal cell growth, but current treatments kill healthy cells, too,” study author Andrew Holland, PhD, associate professor of biology and genetics at Johns Hopkins University School of Medicine in Baltimore, tells Verywell. “For example, the cancer treatment Taxol (paclitaxel) wipes out bone marrow and stem cells, making patients feel weak and causing hair loss."

Cancer-Killing Strategy

Treating cancer can involve surgery, radiation, and traditional chemotherapy, which kills both cancer cells and healthy cells. More recently, targeted therapies have become available. They are more discriminating treatments in that they target specific parts of cancer cells and stop their growth, but although they don’t kill healthy cells, they also may not kill the cancer cells.

The Role of Cell Division in Cancer

As cells age, they replace themselves during a process known as cell division, or mitosis. One structure inside cells, called the centrosome, plays a crucial role in cell division. In order for cells to divide, the centrosome must duplicate itself. Once it does, the two centrosomes then move to opposite ends of the cell. Proteins gather at each centrosome, helping to pull the cell apart into two daughter cells. When a mutation occurs, the process goes awry. Cell division happens too often, produces far too many cells, and results in a tumor.

“Cell division has been targeted before, and many drugs can stop it, but that brings in the toxicity,” William Cance, MD, chief medical and scientific officer for the American Cancer Society in Atlanta, Georgia, tells Verywell.

For instance, a therapy may target a protein in a cancer cell, but that same protein may also exist in normal, healthy cells. So a therapy targeting a protein during cell division (called anti-mitotic targeted therapies) may stop a cancer cell from duplicating, but it may also be toxic to healthy cells, causing side effects.

“Precise mutations need to be discovered and targeted specifically,” Cance says.

To identify strategies that kill cancer cells but spare normal cells, the researchers needed to find a vulnerability in cancer cells and exploit it. And they did. 

A genetic variant called 17q23 is found in cells in 9% of people who have breast cancer, and it makes a protein called TRIM37 more active by amplifying its effect. When TRIM37 is more active, centrosomes do not behave correctly and errors occur during cell division, leading to the overactive cell division that results in tumors.

An enzyme called PLK4 kickstarts the errant cell division process in cells that overexpress TRIM37. The study showed that applying a chemical to block the PLK4 enzyme disrupted centrosomes, essentially killing the cancer cells by keeping them from duplicating. 

“If we remove those centrosomes, the cancer cells cannot survive,” Holland says. “Cell changes can drive evolution, but mistakes allow cells to be vulnerable.”

Identifying Targets for Therapy

To kill cancer cells using a targeted approach, targets must be identified. “That has a potential to open up new classes and new types of cancer drugs in the future,” Cance says.

“A large fraction of breast cancer patients who overexpress the TRIM37 gene will carry the amplification of 17q23,” Holland says. “We absolutely will be able to use the results of this study to develop tests to find people who are likely to respond to a particular therapy."

Using these targets will be similar to what is currently done to test tumors to determine breast cancer subtypes, such as HR-/HER2+, or to perform genetic testing on family members to see if they carry the BRCA1 or BRCA2 gene or another inherited mutation.

“The breast cancer subtype HER2+ is associated with 40% to 50% of cancers that carry the 17q23 amplicon, and also a good number of BRCA1 and triple-negative breast cancers,” Holland says. “The 17q23 amplicon is found in 9% of all breast cancers—about the same as all BRCA patients put together.”

That means of the 325,000 people diagnosed with breast cancer every year, approximately 30,000 of them could benefit from a future targeted therapy based on the interaction of 17q23, TRIM37, and PLK4.

 “The excitement here is for a treatment with a greater therapeutic effect because toxicity would be limited to cancer cells,” Holland says.

Next Steps

This new study contributes to the body of knowledge that will help develop specific tests as well as future therapies, but it is early. Before a new treatment would become available to the public, more exploratory studies would need to be performed. If additional laboratory studies look positive, clinical trials would have to take place to determine the best dose and assess effectiveness and safety. Then, the treatment would go for regulatory review and approval by the Food and Drug Administration (FDA). All of that takes years of work and persistence.

“Cancer cells develop resistance to therapies, such as kinase (enzyme) inhibitors like PLK4. It’s one of the biggest problems in cancer,” Cance says. “This research appears to be a mechanism that spares normal cells. The challenge will be to develop treatments that prevent cancer cells from reprogramming their kinases and continuing to grow.”

Cance says this study opens the door for different types of targeted cancer therapies and new classes of cancer drugs that will not be limited to breast cancer. More discriminating therapies will make treating all types of cancer safer and more effective.

If you are at risk for breast cancer, talk to your doctor about reducing your risk. Although you can’t change your genes or your age, you can be vigilant about addressing risk factors you can control, such as:

What This Means For You

If you or a loved one has breast cancer, this study offers hope for personalized treatments in the future. Know that researchers around the world are working hard to find ways to best target and treat your condition.

  • Limiting alcohol consumptionReducing excess body weightQuitting tobacco useGetting enough exercisePerforming monthly breast self-exams