Louisiana State University: LSU BE, ChE Team Study Drug Resistance In ER+ Breast Cancer Cells

Press release from Louisiana State University:

October 27, 2021

BATON ROUGE, LA – Estrogen receptor-positive (ER+) breast cancer is the most common
type of breast cancer diagnosed today. When someone has ER+ breast cancer, the cancer
cells’ growth is facilitated by the estrogen receptor. In breast cancer, hormone receptors
(proteins located in and around breast cells) signal cancerous cells to grow uncontrollably,
resulting in a tumor.

According to the American Cancer Society, two out of three breast cancer cases are
hormone receptor-positive with 60-70 percent of those cases being ER+. Targeted therapies
exist for ER+ breast cancer, however, nearly half of those patients will become resistant
to endocrine therapy. Thanks to a $140,000 grant from the National Cancer Institute,
two LSU professors and their students are researching what causes this resistance
to treatment.

LSU Biological Engineering Assistant Professor Elizabeth Martin, who is the principal
investigator on the NCI research project, says that while ER+ breast cancer is more
likely to respond to endocrine therapy, 40 percent of ER+ patients become resistant
to this treatment.

Endocrine therapy directly targets the estrogen receptor unlike chemotherapy, which
can target proliferating cells in the body, including healthy cells.

“Either patients already had resistance to the endocrine treatment or acquired it
over time,” Martin said. “Unfortunately, when there is resistance in the ER+ cells,
it can be seen after the cancer cells have metastasized and moved on to another organ.”
 

LSU Chemical Engineering Associate Professor Adam Melvin, who serves as the co-PI
on the project, says that they are not so much studying resistance at the primary
site, but the journey from point A to point B as the cancer cell metastasizes or moves
to another spot in the body.

“The hypothesis we have is that the cancer cells pick up mutations [so that they go]
from being susceptible to endocrine therapy to being resistant,” he said. “How does
it become resistant?”

One thing that could make them change, Melvin added, is fluid shear stress. This occurs
as the cell moves through the vasculature, putting pressure on the cell. Prolonged
exposure to this pressure can cause the cell to mutate, which can make it stronger.
Melvin compares it to someone going down a waterslide where the fluid velocity of
the water puts more pressure on the body.

Martin says the ultimate goal of this research is to understand how to resensitize
cancer cells to endocrine therapy so that patients don’t need to move to treatments
like chemotherapy.

“Metastasizing cancer cells should all consistently experience fluid shear stress,”
she said. “If they’re all experiencing it, it should be activating the same intracellular
pathways in the cells. When the cells get to the final site and don’t respond to endocrine
therapy, you can use whatever pathway shear stress is activating as an additional
target to resensitize the cells to endocrine therapy. So, instead of saying, ‘now
you need chemotherapy,’ we now know what’s being activated in the cells as they’re
metastasizing. So, here are options to resensitize cancer cells to endocrine therapy.”

LSU ChE graduate student Braulio Ortega Quesada of San Pedro, Costa Rica, and LSU
BE graduate student Jonathan Cuccia of Meraux, La., work under Melvin and Martin and
are stressing out the ER+ cells on a micron-scale waterslide, as well as analyzing
them in groups and individually at the end to see how the cells differ from one another.

They run the breast cancer cells through a microfluidic device that shears the cells
and then traps them in an array that can hold up to 7,000 cells, which can be stained
for changes in protein expression. While Quesada analyzes single cells, Cuccia looks
at millions of cells at a time.

Part of Quesada and Cuccia’s research entails taking photos of the cells under a microscope,
which can be time-consuming in the lab. In order to help decrease the amount of time
spent taking photos, Martin and Melvin have assigned a biological engineering senior
design team to create an automated image-capturing system. The six-person team was
divided into a hardware team led by LSU BE senior Morgan Doyle of Madisonville, La.,
and a software team led by LSU ChE senior Adam Langlois of Meraux, La. Other team
members include Jacob Chaisson of Houma, La., Logan Brou of Port Allen, La., Alejandra
Ham of Slidell, La., and Sarah Jimenez of Ponchatoula, La.

“We’re editing the microscope [so that it] can do automated image-capturing that will
allow more time for the grad students to work on other aspects of the project,” Langlois
said. “Right now, Braulio must take photos of the cell groups (3,000 total cells),
which takes an hour. The objective for the automated system will take less time, but
exactly how long is not known yet.”

“I’ve been doing breast cancer research in Dr. Martin’s lab for nearly two years,
so for me, this is a really cool project, and it’s great knowing that what we’re doing
is going to help the grad students progress their research at a faster pace,” Doyle
said.

So far, Quesada and Cuccia are seeing positive results in their labs, which should
give hope to the thousands of ER+ breast cancer patients who are unresponsive to endocrine
therapy at metastatic sites.

“We’ve already seen some pretty promising things that have us excited,” Cuccia said.
“We’re looking forward to where this goes in the future.”

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Contact: Libby Haydel

Communications Specialist

ehaydel1@lsu.edu

225-578-4840

This press release was produced by Louisiana State University. The views expressed here are the author’s own.