Adam P. Jones

NF2-related schwannomatosis (NF2-SWN) is an autosomal dominant tumor predisposition syndrome caused by germline mutations in the NF2 tumor suppressor gene. The disease is characterized by the development of bilateral vestibular schwannomas (VSs), which progressively enlarge and result in hearing loss, imbalance, and ataxia-symptoms that profoundly affect patients' quality of life. No FDA-approved pharmacologic treatments are currently available. Among the neurological deficits, ataxia remains a particularly debilitating yet understudied manifestation, largely due to the lack of robust preclinical models for its evaluation. In this study, we developed a set of behavioral assays to systematically assess tumor-induced ataxia in an orthotopic mouse model of VS-associated hearing loss and ataxia. These tests allow quantitative measurement of balance and motor coordination deficits arising from tumor burden. This experimental platform enables mechanistic studies of tumor-induced cerebellar dysfunction and provides a valuable tool for preclinical evaluation of therapeutic strategies. By integrating behavioral assessments with tumor biology and hearing tests, this approach facilitates the characterization of both tumor-suppressive and neuroprotective treatment effects. Ultimately, these assays offer a versatile framework that can also be applied to other neurological disorders characterized by ataxia, expanding their utility beyond NF2-SWN.

NF2-related schwannomatosis (NF2-SWN) is an autosomal dominant tumor predisposition syndrome caused by germline mutations in the NF2 tumor suppressor gene. The disease is characterized by the development of bilateral vestibular schwannomas (VSs), which progressively enlarge and result in hearing loss, imbalance, and ataxia-symptoms that profoundly affect patients' quality of life. No FDA-approved pharmacologic treatments are currently available. Among the neurological deficits, ataxia remains a particularly debilitating yet understudied manifestation, largely due to the lack of robust preclinical models for its evaluation. In this study, we developed a set of behavioral assays to systematically assess tumor-induced ataxia in an orthotopic mouse model of VS-associated hearing loss and ataxia. These tests allow quantitative measurement of balance and motor coordination deficits arising from tumor burden. This experimental platform enables mechanistic studies of tumor-induced cerebellar dysfunction and provides a valuable tool for preclinical evaluation of therapeutic strategies. By integrating behavioral assessments with tumor biology and hearing tests, this approach facilitates the characterization of both tumor-suppressive and neuroprotective treatment effects. Ultimately, these assays offer a versatile framework that can also be applied to other neurological disorders characterized by ataxia, expanding their utility beyond NF2-SWN.

Ovarian cancer is one of the deadliest gynecological malignancies, where most patients become clinically symptomatic at advanced stages of disease due to the lack of effective diagnostic screening. Despite recent advances in surgical resection and chemotherapy, recurrent ovarian cancer remains largely refractory to treatment, resulting in poor prognosis. The ovarian cancer tumor microenvironment (TME) is highly abnormal and presents a significant barrier to successful therapy. A combination of abnormal vasculature, desmoplastic extracellular matrix, and aberrantly activated hypoxic and immune-suppressive pathways culminates in promoting tumor growth, dissemination, chemoresistance, and immunosuppression. Whilst immune checkpoint inhibitors have shown success in other cancers, their application in ovarian cancer, particularly at advanced stages, remains limited. In this review, we discussed the application of tumor extracellular matrix normalizing therapies in preclinical models of advanced ovarian cancer, and their synergistic benefit to chemotherapy and immunotherapy. Collectively, these insights underscore TME normalization as a promising therapeutic strategy with the potential to improve ovarian cancer management.