Dissecting SOX9-Mediated Cancer Stemness and Immunosuppression for Novel Strategies in Advanced Gastric Adenocarcinoma
Abstract
GAC is a major health burden in the USA and globally. Most patients are diagnosed in advanced stage and have a poor overall survival of <12 months. Therapies are quite limited in the clinic. To address this unmet clinical challenge, we have leveraged our clinical resources and preliminarily revealed that SOX9, a transcription factor required for embryonic development, is highly expressed in primary and metastatic GAC cells and is associated with shorter survival. Genetic knockout (KO) of SOX9 decreased cancer stemness traits and tumor formation in mice, while boost immune response. The main objective of this proposal is to elucidate the functional role and mechanisms of SOX9-mediatedmetastatic niche and immunosuppression in GAC with PC for novel therapeutic discoveries that can translate into clinic trials. We hypothesize thatSOX9 is a metastatic niche factor that mediates tumor immune evasion through autocrine and paracrine effects of LIF that suppresses immune responses and promotes tumor growth/metastases. We plan to elucidate the mechanisms of how SOX9 in tumor cells suppressing T cell functions; and most importantly, we will find the best combinational treatment strategies to target SOX9 high GAC tumors that can be translated to clinic to benefit GAC patients including Military/Veterans/families.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2023
- Accession Number
- AD1216029
Entities
People
- Jaffer A. Ajani
- Shumei Song
Organizations
- The University of Texas MD Anderson Cancer Center