Clinical implications of Wnt signaling alterations in patients (pts) with advanced prostate cancer (aPC)

Autor: Amanda Broderick, Jinju Li, Alec Chu, Clara Hwang, Pedro C. Barata, Frank Cameron Cackowski, Matthew Labriola, Alyssa Ghose, Mehmet Asim Bilen, Deepak Kilari, Laura Graham, Abhishek Tripathi, Rohan Garje, Vadim S Koshkin, Elizabeth Pan, Tanya B. Dorff, Rana R. McKay, Michael Thomas Schweizer, Ajjai Shivaram Alva, Andrew J. Armstrong
Rok vydání: 2023
Předmět:
Zdroj: Journal of Clinical Oncology. 41:229-229
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2023.41.6_suppl.229
Popis: 229 Background: Aberrant Wnt signaling has been implicated in prostate cancer tumorigenesis, progression, and metastasis in preclinical models. While studies have identified recurrent molecular alterations in the Wnt signaling components in about 20% of aPC pts, the clinical significance of these alterations has been incompletely characterized. Methods: PROMISE is a multi-institutional, retrospective, clinical-genomic database - inclusive of aPC pts who had tissue and/or blood-based genomic testing by commercially available CLIA-certified platforms. We evaluated outcomes in pts with alterations leading to the activation of the canonical Wnt pathway, specifically activating mutations in CTNNB1 or RSPO2 or inactivating mutations in APC, RNF43, or ZNRF3 (Wnt altered), compared to those lacking such alterations (Wnt wild type). Multiple endpoints were evaluated, including the frequency of metastatic disease to different sites and co-occurring alterations. Results: 1596 pts with aPC were included with a median age of 63 years at diagnosis. Wnt pathway alterations were identified in 12.4% (198/1596). Wnt altered pts had a statistically significant increase in liver and lung metastases compared with Wnt wild type pts at diagnosis (4.5% vs 2.1%, p=0.0438; 6.1% vs 2.9%, p=0.0292), at first metastatic disease (11.6% vs 5.4%, p= 0.0015; 14.8% vs 6.6%, p
Databáze: OpenAIRE
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