Female Duo Blazes Trail in Cancer Research

Published on August 12, 2020

Shortly after joining Eastern Kentucky University, Dr. Lindsay Calderon, associate professor of biological sciences, and Dr. Margaret Ndinguri, associate professor of chemistry, met at a grant writing workshop.

“From there, we started working together, and it has been a blessing,” Ndinguri said. “A good partner to work with really helps a lot.” “It’s been fun actually,” Calderon said about her research partnership with Ndinguri. “We’ve had a good time.” 

With a united goal of advancing the healthcare provided to patients afflicted with cancer, the pair set out on what has become a life-altering journey. “Our short term plan is to mold the system through our research endeavors and our long term plan is through our students who will become our future physicians,” Ndinguri said. They are reaching their career milestones through a unique interdepartmental collaboration that spans gender, race and background. They said they hope their collaboration is the embodiment of EKU and a model that should be strived for at all universities across the nation.

That first meeting sparked both a personal and professional relationship that, with some luck and continued research, could someday save the lives of men and women with the most difficult-to-treat cancers. The pair is on the cusp of creating a drug that would be considered revolutionary in reproductive cancer diagnostics and treatments. 

Calderon and Ndinguri discovered a chemical compound targeting specific types of cancers. Typical cancer scans target major receptors on the cell surface when diagnosing or treating cancer. But some less common forms of reproductive cancers, including triple negative breast cancer and metastatic ovarian cancer, along with a few other non-reproductive cancers, lack those major receptors. Triple negative breast cancer is one of the most prevalent forms of breast cancer in young women aged 20-34, contributing to 56 percent of African American and 42 percent of white women breast cancer cases. 

“So, it is a disease that afflicts women in the prime of their lives, and the younger you are diagnosed with it the more likely you are to succumb to the disease,” the duo said.  

“It’s the most aggressive and invasive, meaning it has the ability to spread beyond the primary tumor site. It’s called triple negative because it doesn’t have the three major receptors on the cell surface,” Calderon said. “And those receptors are the ones that chemotherapy will target. So that’s why they’re hard to treat, and on top of that, they’re just really aggressive.”

The question became, how do you treat cancers without the typical receptors? The answer was a hormone. The researchers found these cancers tend to overexpress a certain type of hormone receptor, LHRH. 

“We have taken something that is overexpressing, meaning it is mainly found in that tumor,” Ndinguri said. “You will not find that sequence, something like a peptide or protein, prevalent in other normal cells; you will only find that protein in the tumor. If you take a drug and attach it to this protein, then like will go to like.”

Ndinguri’s “like attracts like” explanation serves as the basis behind their diagnostic and therapeutic treatment. Calderon and Ndinguri incorporated LHRH into a diagnostic imaging agent and a chemotherapy drug. With their chemical compound, the hope is these aggressive cancers may be more easily detected and better treated in the future, resulting in higher survival rates.

"Having an ideal diagnostic and treatment in a clinical setting are the two pillars for improving patient lives. So, if we can detect the cancer earlier and then provide a targeted treatment we have then really moved the healthcare pendulum,” Calderon said. “It’s painful to see people who have gone through it, and we just want to help,” Ndinguri said.

Years ago, Calderon and Ndinguri filed a patent for their targeted chemotherapy drug. More recently, they’ve filed another patent for their diagnostic compound as a diagnostic tool, to better detect certain types of cancers. Imaging compounds currently used in medicine aren’t target specific – meaning some cancers could go unnoticed. Just like the therapeutic drug Calderon and Ndinguri developed, the imaging compound goes directly to the cancer cells, allowing doctors the ability to more clearly find and diagnose the cancer.  

“Now we can image the tumors hopefully earlier, and more precisely detect the location better,” Calderon said. “So we’re making an individualized patient regime where we can diagnose it earlier, then give it a personalized treatment.”

Their research focuses on aggressive and invasive forms of cancer – some discriminately affecting young females, ages 20 to 39, and often from ethnic groups. Calderon explained the pharmaceutical industry is less likely to produce or design compounds for a small subset of people. But Calderon and Ndinguri continue to push their discoveries forward. They’re working to complete the many steps and required preclinical trials before their compounds could be used in medicine. 

Serving disadvantaged populations represents a common theme with Calderon and Ndinguri. It’s not only reflected in their research topic, but in their partnership itself as women in science, each from either a minority or underrepresented group, and in their service at EKU. 

Being from the Appalachian region, Calderon said it’s important for her to build the science infrastructure and outreach to the Appalachia community and to those students who are underrepresented. Undergraduate students help in the lab with Calderon and Ndinguri’s research, giving them valuable experiences in science, but also opening up opportunities for medical school or Ph.D. programs.  

“It’s not just about the compound,” Calderon said. “It’s about getting students to be able to learn it and move forward. As they're the next innovators of medicine.”  

For Ndinguri, she’s able to combine her love for teaching and interacting with students with a desire to help people with cancer. “I think the best thing that can ever happen is to just have a cure,” she said.  “That’s the ultimate goal – reduce the pain, get a cure.”

While the duo has made significant progress toward their goals, they are still years away from their discoveries being used in medicine. The hardest part, Calderon mentioned, is hearing from people who need help, and not yet being able to help them. 

“It’s difficult,” Calderon said. “I’ve been emailed by numerous people that have cancer telling me their stories and asking whether I can help them, and that’s just heart-wrenching to me.”