A research team comprised mainly of undergraduate TTU students is producing and analyzing several series of new potent anti-cancer agents based on an existing anti-cancer drug, Triapine, which is undergoing clinical trials around the world. Triapine is a chemical in a class of compounds called thiosemicarbazones, which stop tumor cell growth by blocking enzymes needed for cell replication.
The TTU students are working with chemistry professor Edward Lisic to determine the minimum dosage needed to be effective.
“Most cancer treatments have unpleasant side effects because the drugs kill good enzymes too,” Lisic said. “The student researchers are finding that minor modifications to the chemical compounds can change the efficacy. These new thiosemicarbazone agents may find use in cancer treatment as stand-alone drugs, or in a cocktail of other chemotherapy drugs that work together to inhibit or kill cancer cells and tumors.”
The goal is to produce a compound that attacks over-expressed cancerous enzymes and stops progression of the cancer, without killing the good enzymes.
The TTU students are on the front line of drug development in the labs at TTU, synthesizing series of new compounds and characterizing them using state-of-the-art equipment such as nuclear magnetic resonance spectroscopy and mass spectrometry. The students go to the biology labs, too, and pipe the compounds into cell cultures to screen how effectively the compound is stopping cell growth.
At this point in the research, several potent thiosemicarbazone compounds and their transition metal coordination compounds have been found to have high activity against enzymes that are required for cell replication. TTU is collaborating with two cancer centers, including the Memorial Sloan-Kettering Cancer Center in New York, for further studies and possible testing on patients, especially women with breast cancer. Breast cancer cells over-express a certain enzyme called Topoisomerase II for DNA replication, which is specifically targeted by these new agents.
“We have the personnel and instruments here at TTU that make it work,” said Lisic. “It takes everybody working together, and the students really gravitate to this type of research that affects people’s lives and health.”
Chemistry and biology majors work side by side in the labs, mentored by TTU graduate students and doctoral candidates who have been working with Lisic for a while. Lisic started focusing on the anti-cancer elements of thiosemicarbazone compounds about five years ago.
Along the way, some of the students involved in the work have found their calling. Victoria Holcomb, a spring 2012 graduate of TTU, is going to medical school. Sri Harsha Tummala, who finished a master’s degree in chemistry at TTU in 2012, has a career in the pharmaceutical industry. Elizabeth Melton, a senior majoring in biochemistry, teamed with Holcomb and presented research at the national meeting of the American Chemical Society in San Diego in March.
“The older students mentor the newer ones,” said Lisic. “This grapevine mentoring style holds the students accountable for working together, and it keeps the research moving forward.
“Students are excited to be involved in meaningful research that holds the promise of positively affecting people's lives, and contributing to the overall body of scientific and medical knowledge. I have also seen that the involvement of students in research changes their outlook on life, and helps them focus on their career choices. They become dedicated to their work and to helping others.”