Putting Breast Cancer Cells to Sleep

Xiaoting Zhang in lab

Recently in the lab of Xiaoting Zhang, Ph.D., breast cancer cells were multiplying out of control as usual. Then the unexpected happened—all that tumor-building bustle came to an abrupt halt.

It happened when Zhang, a cancer biologist at the University of Cincinnati College of Medicine, and his research team disabled a protein called MED1. Now they’re trying to uncover the biological mechanisms for how this happens, raising the prospect that a MED1-targeted therapy could be developed to lull breast cancer cells into a permanent sleep, known as senescence.

Senescent cancer cells are still alive but do not divide. They remain dormant until the immune system wipes them out. It’s an indirect cancer-killing approach that harnesses the power of senescence, which Zhang calls “a potent inhibitor of cancer growth.”

Researchers already knew certain chemotherapy drugs could force cancer cells into senescence. They also knew about half of the nearly 233,000 breast cancers diagnosed each year have high levels of the MED1 protein, an aberration that research suggests may spur the growth of breast cancer cells and make them resistant to some hormonal therapies. But until Zhang’s discovery, no one knew turning off MED1 could make breast cancer cells lapse into senescence.

Zhang is now using a four-year, $700,000 grant from the American Cancer Society to figure out how MED1 controls whether a cancer cell subsists or slumbers, and whether eliminating MED1 from breast cancer cells makes them more susceptible to the senescence-inducing effects of certain chemotherapies. His work is also supported by HOPE (Health Opportunity through Partnership in Education) Foundation, a non-profit organization, associated with Washington National Insurance Company of Carmel, Indiana. HOPE has provided $100,000 toward this research.

“Our goal is to enhance the effects of chemotherapy by combining the removal of MED1 with the administration of current chemotherapeutic drugs,” says Zhang. That means patients could potentially overcome drug resistance and experience less severe side effects if lower chemotherapy doses were required, he adds.

Zhang is studying human breast cancer cells grown in the lab that contain different levels of MED1 to better understand the protein’s role in the growth and spread of breast cancer. He’s also observing cancer growth in mice with breast tumors that overexpress MED1 and mice with transplanted human breast tumors that lack MED1 altogether. The mice are then given chemotherapy to see how it affects the growth of tumors.

Treating Breast Cancer With Nanoparticles

Zhang’s team is working on a way to silence MED1 and force rapidly dividing breast cancer cells into senescence. They are having success in mice with a nanotechnology technique that uses microscopic particles called nanoparticles to deliver directly into breast tumors a tiny snippet of RNA that blocks the production of MED1. A nanoparticle is measured in nanometers, with 1 nanometer being a billionth of a meter. (A human hair is about 80,000 nanometers wide).

“RNA nanotechnology is very new, but it’s also very powerful because it can specifically get into cancer cells and shut off whatever protein you want—and it’s not toxic,” Zhang says.

Scientists discovered more than 50 years ago that healthy cells divide a limited number of times before succumbing to senescence. But only more recently did scientists learn this cellular dead end plays a crucial role in cancer. Now they hope to exploit it.

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