Investigators from the UCLA Health Jonsson Comprehensive Cancer Center have identified a protein, called UCHL1, in highly aggressive neuroendocrine carcinomas and neuroblastoma that could potentially be used as a molecular biomarker for diagnosing these cancers and predicting and monitoring responses to therapy.
The team also found that using a UCHL1 inhibitor, either alone or in combination with chemotherapy, significantly delayed the growth and spread of neuroendocrine carcinomas and neuroblastoma in pre-clinical models.
To identify druggable targets for neuroendocrine carcinomas and neuroblastoma, researchers first analyzed publicly available proteomics data and identified UCHL1 as one of the top druggable proteins. The team then investigated UCHL1 levels in tissues from patients with various types of neuroendocrine carcinomas and found elevated levels of UCHL1 in neuroendocrine prostate cancer, lung carcinoid, small cell lung cancer, neuroblastoma, and other neuroendocrine neoplasms. This suggested that UCHL1 may be a common target for drug development in neuroendocrine cancers based on its higher expression in these tumors compared to non-neuroendocrine tissues. The team then tested the therapeutic potential of blocking UCHL1 in pre-clinical models of neuroendocrine carcinomas and neuroblastoma.
The study was published in the journal Cell Reports Medicine.
