Imaging Technology Reveals Small Molecule Compounds That Kill Tumor Cells
University of Pennsylvania School of Medicine researchers have discovered small molecule compounds that are able to perform the functions of a gene commonly mutated in many types of cancer using a newly developed drug screen.
The researchers combined molecular imaging techniques with human cancer cell culture and animal model approaches and were able to reveal the ability of the compounds to kill human tumor cells.
p53 is a tumor suppressor gene widely mutated across all types of cancer. Not only does mutation in the p53 gene cause aggressive tumor growth but also contributes to chemotherapy and radiotherapy resistance.
Developed in the laboratory of Wafik S. El-Deiry, MD, PhD (Professor in the Departments of Medicine (Hematology/Oncology), Genetics, and Pharmacology, UPHS), the small molecule drug screen used in the study 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.
This drug screen allowed the researchers to trace the activity of small molecules in p53-mutant cancer cells.
“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,” explains El-Deiry.
“Our work provides a blueprint for how molecularly targeted therapy can be discovered using new optical imaging technology,” states El-Deiry. “This is very important going forward in the era of molecular medicine and individualized therapy for cancer patients.”
The UPHS research team plans 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, in the hope of bringing new anti-cancer agents to the clinic.
Read more at UPHS.
In Photo: Screening many classes of compounds for activity of small molecule candidate drugs in p53 mutant cancer cells. Using light-emitting reporter genes and imaging technology the investigators were able to detect which compounds restored p53-responsivity and killed the mutant cancer cells. (Credit: Wafik El-Deiry, MD, PhD, University of Pennsylvania School of Medicine; Proceedings of the National Academy of Sciences)
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