Cancer Research Drives Dr. Theodoraki

Caitlin Burns

Dr. Maria Theodoraki

Assistant Professor of Biology
Courses:
General Biology I, Microbiology, Cancer Biology, and Faculty Sponsored Research
Expertise: Molecular Chaperones
Advice for Students: "If you are persistent on working in cancer research, make sure your heart is in it. There is a lot of stress from competition, [but] if you can handle the pace, it’s exciting."

"It’s the personalized aspect [of cancer treatment] that we are missing and need to develop.

- Dr. Maria Theodoraki

Dr. Maria Theodoraki at her desk.
“I don’t think that we will ever have a silver bullet to cure cancer,” said Dr. Maria Theodoraki, assistant professor of Biology, scrolling through a recent presentation about research she’s conducted with Arcadia University Biology students for inflammatory breast cancer, a fatal form of the disease. 

Though there is no targeted treatment plan for a patient diagnosed with inflammatory breast cancer, Dr. Theodoraki’s research is exploring how two compounds derived from Garcinia hanburyi, a species of evergreen tree, could help target these specific cancer cells. While she’s hopeful that this could one day help patients with inflammatory breast cancer live longer or go into remission, Dr. Theodoraki doesn’t believe it’s a panacea for cancers.

Garcinia hanburyi produces the organic GBA compound, which studies in China have shown to have “a positive impact” on cancer treatment. Dr. Theodoraki’s team of student researchers works with synthetic derivatives of this compound, including MAD28 and DAP19, which have so far shown an increased ability to kill different types of aggressive breast cancer. 

What Is Inflammatory Breast Cancer?

According to MD Anderson Cancer Center, inflammatory breast cancer makes up only one to five percent of breast cancer diagnoses. However, nearly 100 percent of the women with inflammatory breast cancer have lymph node involvement, and about 25 percent of them have distant metastases at the time of diagnosis. Inflammatory breast cancer has a poor prognosis, with only a 40 percent five-year survival rate due to its metastatic nature and absence of targeted therapies.

Unlike other forms of cancer, a lump is not always present. Symptoms usually start as a suddenly sore and swollen breast, and progress to:

  • Discoloration of the skin on the breast

  • Dimpling of the breast skin and orange peel appearance

  • Ridges and thickened areas of the skin on the breast

  • Warm, tender, or sensitive to the touch breast

Similar symptoms may be caused by other health problems. However, it’s important to discuss any symptoms you experience with your doctor.

“Cancer is a group of diseases—it’s an umbrella term,” said Dr. Theodoraki. “So, it’s the personalized aspect that we are missing and need to develop. Instead of saying you have a specific type of breast cancer, the idea would be to get a piece of tissue through a biopsy and section it into very small pieces to expose the cancer cells to different therapeutics to see which one has the best effect.”

Originally from Crete, Greece, Dr. Theodoraki found her love of biology in high school and later discovered an interest in molecular chaperones while doing lab work as an undergraduate student at Greece’s University of Patras, where she earned baccalaureate and doctoral degrees in molecular biology. After enjoying success in her early career in seeing how molecular chaperones function to protect other proteins in the cell under normal and stress conditions, Dr. Theodoraki’s post-doctoral research focused on a more translational aspect of investigating the role of molecular chaperones in different diseases. When the cellular quality control system—composed of molecular chaperones, including HSP90—fails, toxic protein deposits form, possibly leading to Parkinson's, Alzheimer’s, or other neurodegenerative diseases. In contrast, cancer cells often rely on hyper-active molecular chaperones in order to maintain their uncontrolled proliferation and ability to spread.

Following her time in Greece, the trilingual Dr. Theodoraki—she speaks English, French, and Greek—served as a postdoctoral research fellow at Mt. Sinai School of Medicine in New York before becoming a research associate at City College of New York, where she also taught. She joined the faculty at Arcadia in 2014, transitioning into a full-time assistant professor position and starting the research lab with three student assistants the following year. 

Throughout her career, Dr. Theodoraki has continued to study how molecular chaperones can be used as targets for the treatment of cancer and explored sensitivities of aggressive breast cancer cell types to different small molecule inhibitors. In a recently published study (see below) where she was lead author, MAD28 was shown to be able to eradicate the compact spheroids composed of inflammatory breast cancer cells in contrast to the currently used chemotherapeutics. 

As the 2017 recipient of the Ellington Beavers Fund for Intellectual Inquiry faculty award, Dr. Theodoraki proposed to further study the molecular mechanisms underlying the therapeutic response of the inflammatory breast cancer spheroids to MAD28. As research on inflammatory breast cancer has progressed, student researchers in her lab have continued to screen and evaluate the activities of compounds similar to GBA and MAD28. Results from their studies identified new compounds that are active against inflammatory breast cancer spheroids and showed that MAD28 can target cells that are hiding deep in the inflammatory breast cancer spheroids. These results were published in 2019 (see below).

Dr. Theodoraki with students in the lab

Dr. Theodoraki works with Biology students Tanis Dorwart '20 and Olivia Stroble '21 in the lab.

Dr. Theodoraki and students continue to run a variety of tests with the compounds in cells representing different types of breast cancer. A Capstone research thesis last year showed that the cancer cells treated with MAD28 and DAP19 lose their ability to migrate, suggesting that treatment of patients with these drugs may reduce or even stop cancer cells from metastasizing. In a continuation of this project, a new Capstone thesis will test if the compounds have similar effects when cancer cells are treated in a 3D model, rather than a monolayer sample. This invasion test uses a gel layer to see how cells spread with or without treatment and provides a more representative model of how the compounds would work inside the tissues of living organisms.  

Other projects in Dr. Theodoraki’s lab include transforming cells traditionally growing as monolayers to 3D spheroids and studying how this change affects the cells’ sensitivity to MAD28 and DAP19, illustrating how these compounds kill different breast cancer cells, and if they induce formation of reactive oxygen species. While the lab has tested non-cancer cells for their reaction to MAD28, similar studies are being performed for DAP19 to explore how this compound reacts in the body if used as a treatment—such as, if the compound only impacts cancer cells or if it would be detrimental to healthy ones, and how it works overall.  

However, Dr. Theodoraki said, their research is merely a petri dish sampling. The next steps for testing the compounds would be to study how they work in animals injected with similar breast cancer cells, which must be conducted in a special lab that could host immunocompromised animals, which Arcadia does not have. If analysis after animal testing shows positive results, the following steps would be clinical trials in humans. 

“Research has to generate new knowledge,” said Dr. Theodoraki. “It cannot be anything but innovative, and we have two things going for us: The inflammatory breast cancer spheroids we study come from a unique animal model that accurately represents this type of cancer and was established by our collaborator.  Additionally, the compounds we use do not exist in the market, but have to be synthesized by another collaborator. I am lucky to work with such great collaborators and students.”

 

Recommended Resources

Research conducted by Dr. Theodoraki and alumni Theodore E. Habarth Morales ’19 and Aspen La-Riene Settle '19 about the effectiveness of MAD28 and MAD67 killing 3D breast cancer spheroids in vitro.

Science Direct

Research conducted by Dr. Theodoraki, students, and alumni about MAD28 and other compounds being promising leads against chemoresistant and metastatic cancers.

Science Direct

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