W81XWH1810581 (Project)

Description:The autonomic nervous system is comprised of two branches, more commonly known as the “fight or flight” sympathetic branch and the “rest and digest” parasympathetic branch, that both send and receive information from the brain. These two branches communicate with every organ in the body and are responsible for maintaining proper organ function. It was once believed that breast tumors did not contain these nerves. However, a recent study with human breast tumors found nerves do exist but only in malignant tumor types and not benign tumors. More interesting, it was observed that greater malignant tumor grades had greater number of nerves found within the tumor. Research using tumor-bearing animals has shown that increasing and decreasing the activity of these two nerve branches with surgical or chemical means has an effect on tumor growth and metastasis. However, none of these research studies directly measured the neural activity to ascertain the degree to which the neural activity changes effect tumor growth and metastasis. The Principal Investigator (PI) for this proposed research is a renowned leader in neural interfacing and has significant expertise in recording neural activity within these two nerve branches. Recently, the PI’s lab has developed and implanted novel electrodes that are 10 times smaller in diameter than a human hair and has recorded neural activity directly from these autonomic nerve branches. Collaborating with two co-PIs who both have extensive expertise in cancer research and clinical cancer treatment, these novel electrodes were implanted in breast tumor-bearing mice and, for the first time, neural activity was recorded within tumors. More importantly, recording the neural activity until metastasis occurred revealed a consistent pattern in the activity level that was observed in every subject. Through other experimental means, this collaboration has confirmed that a neural connection exists between the breast tumor and the brain though the main nerve of the parasympathetic branch called the vagus nerve. This research will perform experiments using two different mouse cancer models (triple-negative and HER2+) which have been found to carry the poorest clinical prognosis and will address two overarching challenges by focusing on the interaction between the autonomic nervous system and the breast tumor: (1) Create an indicator of breast cancer tumor growth and metastasis by recording neural activity within a breast tumor and (2) develop a more effective and less toxic treatment regimen compared to existing treatment options by vagus nerve stimulation (VNS).

Abbreviation:SPARC_W81XWH1810581