Abstract
Abstract Y-box binding protein-1 (YBX1) is a multifunctional protein that regulates genes by binding to their DNA and/or RNA. YBX1 is known to contribute to tumorigenesis, disease progression and resistance by stabilizing the mRNAs of genes that are involved in cell growth and survival. High expression of YBX1 has been associated with poor clinical outcomes and decreased overall survival in over 20 cancer types including lung cancer. Given its critical roles in cancer progression and significant correlation with poor cancer prognosis, we hypothesized that inhibition of YBX1 may sensitize the cancer cells to chemotherapeutic agents. To profile the relationship between YBX1 and chemo-response, we aim to investigate the synergistic effect of YBX1 inhibition with standard of care chemotherapy drugs including cisplatin, in lung cancer using animal models and omics analysis. Our studies have found that SU056, a small molecule YBX1 inhibitor, effectively inhibits YBX1 expression in human lung adenocarcinoma cell lines and halts their cell proliferation and clonogenic potential, whereas overexpression of YBX1 promotes cell proliferation. SU056-mediated YBX1 inhibition also led to G2/M cell cycle arrest in these cells followed by apoptotic cell death. These results were further confirmed in A549 lung tumor xenograft model, where inhibitor treatment delayed tumor progression. We will present collective data from in vitro and in vivo studies with YBX1 inhibitor, combination studies with known chemotherapeutic drugs and omics analysis to suggest that targeting YBX1 has therapeutic potential to increase the efficacy of chemotherapeutic agents. Citation Format: Jee Min Lee, Sanjay Malhotra. Suppressing YBX1 with a small molecule inhibitor sensitizes lung cancer to chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 513.
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