Combination of HDAC and FYN inhibitors in synovial sarcoma treatment.

The SS18-SSX fusion protein is an oncogenic driver in synovial sarcoma. At the molecular level, SS18-SSX functions as both an activator and a repressor to coordinate transcription of different genes responsible for tumorigenesis. Here, we identify the proto-oncogene FYN as a new SS18-SSX target gene and examine its relation to synovial sarcoma therapy. FYN is a tyrosine kinase that promotes cancer growth, metastasis and therapeutic resistance, but SS18-SSX appears to negatively regulate FYN expression in synovial sarcoma cells. Using both genetic and histone deacetylase inhibitor (HDACi)-based pharmacologic approaches, we show that suppression of SS18-SSX leads to FYN reactivation. In support of this notion, we find that blockade of FYN activity synergistically enhances HDACi action to reduce synovial sarcoma cell proliferation and migration. Our results support a role for FYN in attenuation of anti-cancer activity upon inhibition of SS18-SSX function and demonstrate the feasibility of targeting FYN to improve the effectiveness of HDACi treatment against synovial sarcoma.

Re-examining popular screening measures in neuro-oncology: MMSE and RBANS.

BACKGROUND: The Mini-Mental Status Examination (MMSE) is routinely used in neuro-oncology clinics to rule out cognitive impairment. However, the MMSE is known to have poor sensitivity to mild cognitive impairment, raising concern regarding its continued use. More comprehensive cognitive screeners are available, such as the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and may be better able to assess for cognitive dysfunction. METHODS: This retrospective cross-sectional study compared the relative rates of impairment using the MMSE-2 and RBANS in a sample of neuro-oncology patients (N = 81). A preliminary analysis of the sensitivity and specificity of the MMSE-2 to the level of cognitive impairment identified on the RBANS was conducted; in addition, we examined whether an adjustment of the MMSE-2 cut-off score improved consensus with a positive screening on the RBANS. RESULTS: The MMSE-2 failed to identify over half of the patients with cognitive dysfunction that were identified on the RBANS. Further analysis showed limited sensitivity of the MMSE-2 to the level of impairment detected on the RBANS, and an adjustment of the cut-off score did not improve the sensitivity or specificity of the MMSE-2. CONCLUSIONS: These results provide caution for neuro-oncology clinics using the MMSE. If providers continue to rely on the MMSE to screen for cognitive impairment alone, they may fail to identify individuals with mild cognitive impairments.