By combining molecular imaging techniques with human cancer cell culture and animal model approaches, the researchers were able to reveal the ability of the compounds to kill human tumor cells. These findings emphasize the growing role of imaging technology in aiding researchers in the development of individualized cancer treatments.
p53, a tumor suppressor gene, is widely mutated across all types of cancer. In addition to causing aggressive tumor growth, a mutation in the p53 gene contributes to chemotherapy and radiotherapy resistance. In search of methods to combat treatment-resistant tumors, the University of Pennsylvania researchers employed molecular imaging techniques to evaluate the ability of small molecules to produce normal p53 function in the p53-deficient and p53-mutant cancer cells.
The small molecule drug screen was created by inserting firefly luciferase, a reporter gene capable of emitting light, into human tumor cells carrying the p53 mutation, and observing the subsequent response.
“Just as fireflies emit light that we can see with our eyes, the cancer cells were engineered to emit light if a p53-like response was triggered by any of the small molecules that we examined,” explained Dr Wafik El-Deiry, professor in the university’s departments of medicine (hematology/oncology), genetics, and pharmacology.
The light emissions displayed by the live cell imaging instrumentation revealed which molecules were able to achieve p53 responses in the abnormal cancer cells. Further testing exposed the ability of high doses of several groups of the small molecules to kill human cancer cells in cell culture and in mouse models implanted with human tumors.
“Our work provides a blueprint for how molecularly targeted therapy can be discovered using new optical imaging technology,” stated Dr El-Deiry. “This is very important going forward in the era of molecular medicine and individualized therapy for cancer patients.”
In the future, the researchers to continue to explore the therapeutic effects of the small molecule compounds in different types of cancer and to evaluate the potential toxicities of these compounds. Ultimately, the group hopes to bring new anticancer agents to the clinic.