Multi-modal omics analysis identifies targetable sensory neuron circuitry that promotes sarcoma disease progression

Osteosarcoma Webinar Series: Sowmya Ramesh, PhD joins us on OsteoBites to discuss how multi-modal omics analysis identifies targetable sensory neuron circuitry that promotes sarcoma disease progression.Bone pain is a hallmark of bone cancers, including osteosarcoma (OS), mediated by skeletal-innervating peripheral afferent neurons. However, the roles of tumor-associated sensory neurons in OS beyond pain perception remain poorly understood. To investigate their regulatory functions, a chemical-genetic approach was employed in mice carrying a knock-in allele for TrkA to perturb sensory nerve innervation during OS growth and progression. TrkA inhibition in these transgenic mice significantly reduced sarcoma-associated sensory innervation and vascularization, altered tumor-associated macrophage polarization, decreased tumor growth and metastasis, and extended overall survival.These findings suggest that targeting pathological innervation in OS may serve as an adjunctive therapy to enhance clinical outcomes and survival.Dr. Ramesh is a postdoctoral researcher from the James lab at Johns Hopkins. The lab's research focus lies at the intersection of skeletal pathophysiology and stem cell biology. The lab looks at the interaction of nerves in various musculoskeletal repair including bone repair and regeneration, osteoprogenitor cell characterization, and neoplastic bone. Dr. Ramesh specifically works on understanding how peripheral nerves regulate osteosarcoma disease progression.