C. Patience Masamha has dedicated her research to fighting cancer by discovering new drug deliveries at the molecular level. The Assistant Professor of Pharmaceutical Sciences’ new project will tackle ovarian cancer and its tendency to return after initial, successful chemotherapy.

The project is based on preliminary ovarian cell research done by Masamha and two graduate students, Zach Todd and Bettine Gibbs ’19.

“Patients who usually respond to chemotherapy drugs will, at some point, develop resistance to those drugs,” says Masamha, who chose to study cancer after her grandfather passed away from mantle cell lymphoma. “Once the patient is diagnosed, they usually go through surgeries and aggressive chemotherapy. Patients usually respond well to treatment, but the cancer often comes back. And when it comes back, it’s resistant to the original chemotherapy.”

In January, Masamha received a $10,000 New Investigator grant from the American Association of Colleges of Pharmacy to fund the work. The project will explore why ovarian cancer is so drug-resistant, especially compared to other cancers. The goal is to develop a new drug that will make cancer cells more sensitive to chemotherapy, lowering the chance of relapse.

Masamha is looking at drug transporter proteins, which are the body’s natural way of removing toxins from healthy cells. But cancer hijacks this system, repurposing those toxin-removing proteins to pump chemotherapeutic drugs back out of cancerous tumor cells—reducing the treatment’s effectiveness and resulting in a drug-resistant disease. Masamha wants to know how these drug transporters are produced in order to later develop drugs that target these transporters to stop refluxing drug molecules in the cells of ovarian cancer patients.

Masamha says there is conflicting information in her field about these proteins. Some papers state the drug transporter concentrations are high in ovarian cancer patients, while other researchers say the same proteins are too low in the patients. Masamha’s research aims to provide more understanding of how these proteins behave under the influence of cancer.

Masamha’s research focuses on messenger RNA (mRNA), which reads DNA codes from the drug transporter genes to help the body create proteins. Different forms of mRNA can be made from the same DNA sequence. When cancer is present, the cells overproduce shortened mRNAs, which behave in a way that leads to the spread of cancer. Masamha is trying to figure out how short and long mRNAs can be made from the same DNA sequence, with the goal of creating a drug that would help prevent production of short mRNA.

The shorter mRNAs in cancer cells—which would need to be destroyed to prevent chemotherapeutic drugs from being kicked out of the cell—aren’t always detected by current treatment methods. Masamha’s group is working on ways to better detect those affected molecules, and to figure out how cancer cells generate these shorter mRNAs in the first place.

“If we are able to detect those short mRNA messages, that would clear up conflicting information in the field about these proteins,” she says. “We want to develop drugs that prevent the shorter mRNA from being produced in cancer cells. This will reduce the amount of drug transporter proteins that are made by tumor cells, allowing anti-cancer drugs to work.”

Zach Todd has been working in Masamha’s lab since fall 2016. He says focusing on the mRNA activity within cancer-affected cells could lead to a new way to treat cancer—helping healthcare providers stay a step ahead of the disease.

“Sometimes cancer has the annoying habit of figuring things out faster than we can,” Todd says. “We have to work around it, and this project is very promising.”

Photos by Brent Smith

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