Individual tumors respond differently to cancer drugs, if at all. Until now, it remained a mystery why tumors have different reactions to the exact same therapy. But a new study at the USC Viterbi School of Engineering finds that tumor growth properties can influence response to cancer drugs.
"Identifying a measurement or quantity that predicts how specific tumors will respond, called a predictive biomarker, is extremely valuable to cancer research," said Stacey Finley, a USC assistant professor of Biomedical Engineering and co-author to the study. Finley, a Gordon S. Marshall Early Career Chair, is also a faculty member of the new USC Michelson Center for Convergent Bioscience.
Tumors exploit a biological process called angiogenesis, which is the formation of new blood vessels from pre-existing ones. In order to grow and multiply, tumors source nutrients delivered by this new vasculature. But tumor growth will slow down if proteins like vascular endothelial growth factor (VEGF), an angiogenesis promoter, are waylaid.
The research team used a computational model of tumor-bearing mice (verified by published experimental data) to investigate response to VEGF-inhibiting drugs and how this response is affected by tumor development. The model illuminated that certain properties of tumor growth help forecast whether drug therapy will thwart tumor expansion.
"We found that certain parameters about the way the tumor grows could successfully and accurately predict the response to anti-angiogenic treatment that inhibits VEGF signaling in the mouse," Finley said. "Using the characteristics of the tumor's growth, we can predict how effective the anti-angiogenic therapy will be, or whether the tumor's growth will slow down, even before treatment begins."
A next step in the research includes a mathematical model to simulate a virtual population of mice randomly assigned different tumor growth parameters. The model will mimic tumor growth with and without drug therapy- and be able to predict mice who respond to drug therapy (resulting in slower tumor growth) and mice with no effect. The research team will further use experimental data to validate the model's predictions.
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The study received funding from the US National Science Foundation. As well, the USC Provost's Office provided support in the form of an Undergraduate Research Fellowship granted to the study's lead author, Thomas Gaddy.
In addition to Gaddy and Finley, co-authors include Qianhui Wu and Alyssa Arnheim. The research, titled "Mechanistic modeling quantifies the influence of tumor growth kinetics on the response to anti-angiogenic treatment" is featured in PLOS Computational Biology.
About the Michelson Center for Convergent Bioscience
The USC Michelson Center for Convergent Bioscience brings together a diverse network of premier scientists and engineers under one roof, thanks to a generous $50 million gift from orthopedic spinal surgeon, inventor and philanthropist Gary K. Michelson, and his wife, Alya Michelson. At the Michelson Center, scientists and engineers from the USC Dornsife College of Letters, Arts and Sciences, USC Viterbi School of Engineering and Keck School of Medicine of USC are working to solve some of the greatest intractable problems of the 21st century in biomedical science, including a fundamentally new understanding of the cell and new approaches for cancer, neurological and cardiovascular disease.
USC Viterbi School of Engineering
Engineering Studies began at the University of Southern California in 1905. Nearly a century later, the Viterbi School of Engineering received a naming gift in 2004 from alumnus Andrew J. Viterbi, inventor of the Viterbi algorithm that is now key to cell phone technology and numerous data applications. One of the school's guiding principles is engineering +, a term coined by current Dean Yannis C. Yortsos, to use the power of engineering to address the world's greatest challenges. USC Viterbi is ranked among the top graduate programs in the world and enrolls more than 6,500 undergraduate and graduate students taught by 185 tenured and tenure-track faculty, with 73 endowed chairs and professorships.
Journal
PLoS Computational Biology