Summary
This research project investigates the mechanisms driving neuroendocrine prostate cancer (NEPC) development and metastasis, focusing on the roles of deregulated IL-1β production and Mic60-low mitochondrial signaling as potential therapeutic targets.
What they want
Project 2 aims to elucidate how deregulated interleukin-1β (IL-1β) production and Mic60-low mitochondrial signaling reprogram plasma membrane dynamics of cell motility, modulate kinase and Rho GTPase activation, sustain spatiotemporal bioenergetics, and increase the dissemination of circulating tumor cells in vivo. The project will also characterize the role of this pathway in shaping an immune-inflammatory NEPC microenvironment via NFκB activation and intratumoral recruitment of immunoregulatory lymphoid and myeloid cell subsets, and credential novel therapeutic vulnerabilities in genetic and syngeneic preclinical NEPC models in vivo.
Deliverables
- Elucidation of mechanisms by which IL-1β and Mic60-low mitochondrial signaling influence NEPC cell motility, bioenergetics, and circulating tumor cell dissemination
- Characterization of the pathway's role in shaping the immune-inflammatory NEPC microenvironment
- Credentialing of novel therapeutic vulnerabilities in preclinical NEPC models
- Identification of actionable therapeutic targets for therapy-induced NEPC
Technical requirements
- In vivo experiments
- Genetic preclinical NEPC models
- Syngeneic preclinical NEPC models
