I-Corps: Model-driven precision oncology for cancer therapy design

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The broader impact/commercial potential of this I-Corps project is the creation of clinical decision support software that will enable oncologists to apply precision medicine to improve cancer survivor rates while minimizing the risk of chemotherapy-induced peripheral neuropathy. Chemotherapy-induced peripheral neuropathy is a common cancer treatment side effect that causes persistent sensory impairments accompanied by pain that often results in dose limitation or even treatment discontinuation. As cancer survivor rates improve, the prevalence and economic impact of chemotherapy-induced peripheral neuropathy is expected to increase. There is a critical need for effective preventative strategies to be developed. Using the clinical decision support software developed with this I-Corps project, oncologists may increase cancer survival rates at the 5-year mark by avoiding neuropathy-related detrimental dose reduction or treatment discontinuation. Oncologists may also improve their patient's quality of life (e.g., decrease pain and disability while increasing activity level) by reducing the risk of chemotherapy-induced peripheral neuropathy. By alleviating chemotherapy-induced peripheral neuropathy, medical costs are expected to be reduced as well.This I-Corps project may improve clinical decision making by applying model-based precision oncology. Cancer is an umbrella term for diseases that are associated with the loss of cell-cycle control, the mechanism that tightly regulates cell numbers by maintaining the right balance between cell proliferation and cell death. This loss of cell-cycle control usually manifests itself as a malfunction in the cellular signaling networks. For the vast majority of cancers, there is a critical need for the precise identification of the failure points in the various signaling networks, with the goal of targeting therapy with a better likelihood of success. This I-Corps project utilizes gene regulatory network models to identify key drug targets to kill cancer cells in several aggressive cancer lines (e.g., pancreatic, breast, lung, osteosarcoma and metastatic melanoma). New network models will be created that incorporate both cancer signaling networks as well as networks for the development of chemotherapy-induced peripheral neuropathy. Designing treatment plans to address both cancer and neuropathy benefits from the model-based precision oncology approach developed in this I-Corps project.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.