Could a Cardiac Drug Stop Breast Cancer Metastasis?

Mentorship while fighting cancer: Madeleine Oudin and Deepti Srinivasan

Triple-negative breast cancer is notoriously hard to treat. Assistant Professor Madeleine Oudin’s lab at the School of Engineering studies how to tame those cancer cells into submission. With Laidlaw Scholar Deepti Srinivasan, a senior biomedical engineering major and an aspiring physician, Oudin investigated how manipulating potassium channel activity could alter those cells’ bioelectric signals—making the cancer less likely to spread.

In the process, they determined that an FDA-approved anti-arrythmia drug, amiodarone, could alter cells in the same way.

Their newly published work is poised to make waves in the field, ideally making a difficult cancer easier to treat.

“The lab got a large grant from the NIH to continue to work on the electrical properties of tumors. This work helped establish us in the field,” Oudin says. Oudin is the Tiampo Family Assistant Professor of Biomedical Engineering.

The Problem: Stopping the Spread of Cancer

Oudin: The focus of my lab is to understand cancer metastasis, which is the dissemination of primary tumor cells to other organs in the body. Patients rarely die from their primary tumor, but often from tumors that form in other organs. I wanted to understand why these cells can spread throughout the body. How does this impact response to current therapies? Can we potentially identify new therapies to treat progression and allow people to live longer?

The Backstory: Helping Patients—With a Personal Connection

Oudin: I thought about going to medical school, but then I discovered research. I really loved being able to visualize cells using methods like microscopy and studying their properties. I initially studied how cells move around in the brain—but then I thought cancer was a better way to apply my knowledge and to help patients down the line.

Srinivasan: When I came across Professor Oudin’s lab, it really stood out. My grandma died from triple-negative breast cancer that recurred. It was chemotherapy-resistant. It was gratifying to work in research that I personally knew was lacking.

Oudin: In engineering, there usually aren’t as many labs run by women, and there are traditionally fewer women in leadership positions. I’ve worked with about 30 undergrads, and 28 of them have been women. I like to show them, as a woman, that you can speak up and succeed.

The Burning Question: Can We Change Cells to Make Them Less Metastatic?

Oudin: This research focuses on the electrical properties of tumor cells. There’s been some evidence that tumor cells have different electrical properties than healthy cells. If we can we tune the electrical properties of tumor cells, can it impact how metastatic they are? Can we find treatments that change these electrical properties to make them less metastatic?

Srinivasan: At first, we were trying to figure out which ion channels were relevant in controlling the bioelectric properties of cancer cells. A lot of that was done using a voltage-sensitive dye that changed color in response to changes in the cell’s voltage. It was really interesting to see that we could collect these images in bulk.

But then we wondered: How do we analyze these images—because they’re just a visual—to get solid, quantitative data? A lot of the work that I did early on was figuring out how to analyze cells individually.

Triumphs and Cliffhangers: A Negative Cell with A Positive Outcome

Oudin: We used methods to make cells either more negative or more positive. It had been shown that cancer cells were more positive, but we didn’t know if this impacted their ability to spread. And we thought making them more negative would make them less likely to metastasize.

We saw the complete opposite, and it was a huge shocker. The tumors grew like crazy when we made them more negative. They metastasized more than I’ve ever seen for any mouse experiment we’ve ever done. We were able to understand how just changing the electrical properties really changes so much about the tumor cells. That’s really something that no one in the field had appreciated.

Srinivasan: There were proud moments along the way. In our first set of experiments, we found out potassium was the most relevant player in metastasis. It wasn’t what we expected, but we had a result that was convincing because of the data. Publishing a paper on this, and tying the whole story together, was extremely satisfying.

The Collaboration: Symbiosis

Oudin: Tufts undergrads are a big part of our research enterprise. Deepti is able to do so much. She’s just so organized, so efficient, and can handle so many things. Everything she does is so well-done, so rigorous, so well thought-out. She’s now TA’ing in one of my classes, and I know I can count on her to educate the next generation. She’s inspiring for students, and a kind, patient mentor. We could not have finished the last experiments for the publication process without her.

Srinivasan: Professor Oudin has been amazing. She’s taught me so much about what it means to be a professional. When I first started in the lab, I was pretty young and not the most organized person. Having structure, having these experiments to do, and getting feedback and thinking through science with her taught me to be more meticulous, which I use in every aspect of my academics. She also taught me how to think critically, which is something that’s been really special. She’s always asking: Why? Why are we seeing what we’re seeing? I’ve started to ask similar questions.

The Outcome: A Safe Heart Drug with Cancer-Curing Potential

Oudin: We screened drugs known to change the electrical properties of other cells, and we found one, amiodarone, that helps to make cells more positive in the context of heart disease. We applied this to our cancer cells and mouse models, and you could see that the drug decreased metastasis. That was really cool, because: Here’s a drug we know is safe. It’s already FDA-approved. Actually getting it to patients could happen a lot more quickly than starting from scratch.

I’ve now had breast cancer patients e-mail me to ask: “When can I take this?” Being able to repurpose drugs provides a lot of hope.

In a word, this partnership was…

Oudin: Rewarding.

Srinivasan: Rewarding! And so we don’t say the same thing: enriching!

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