Mechanisms and Consequences of Hedgehog Signaling and Immune Infiltration in Schwannoma
Abstract
Neurofibromatosis is a complex genetic disorder leading to multiple cancers. Schwannomas, which are among the most common cancers affecting neurofibromatosis patients, are tumors arising from nerves that course throughout the body. Although schwannomas are typically slow growing and have excellent rates of long-term control after treatment with surgery or radiation, schwannomas cause debilitating pain from nerve injury that can be permanent and can be exacerbated by existing therapies. Thus, there is an urgent, unmet need for new treatments for neurofibromatosis patients with schwannomas. The objective of this proposal is to determine whether drugs that block the molecular mechanisms underlying schwannoma are effective treatments for cancer growth or cancer pain in neurofibromatosis patients. By studying human schwannoma samples, we have identified two previously unknown molecular mechanisms that we hypothesize drive schwannoma growth and pain. To test this hypothesis, we will use genetics and drugs that block these molecular mechanisms to treat mice with schwannomas. We will measure tumor growth and pain in mice to establish preclinical rationale for new clinical trials to treat cancer and cancer pain in neurofibromatosis patients with schwannomas. The drugs we will investigate are FDA-approved, have minimal side effects, and have no potential for abuse or addiction. This strategy will lower the risk of adopting the targets we validate in future research projects and clinical trials. Thus, we anticipate that the data from this project will be ready to translate to neurofibromatosis patients immediately at the conclusion of the award period. In summary, we are using genetics, pharmacology, and mouse models to study the biology and treatment of schwannoma. Successful completion of this project will elucidate molecular mechanisms underlying the most common cancer of the peripheral nervous system and shed light on improved treatments for cancer and cancer pain in neurofibromatosis patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110662
Entities
People
- David Raleigh
Organizations
- United States Army
- University of California, San Francisco