Presentation Type
Poster
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
Hepatocellular carcinoma (HCC) stands as the prevalent form of primary liver cancer worldwide, diagnosing over half a million new cases annually. Surgical interventions like hepatectomy and liver transplantation offer a potential cure for early-stage HCC. However, the prognosis for advanced stages remains grim due to drug resistance, particularly with high refractoriness rates. Sorafenib, a tyrosine kinase inhibitor, is an approved treatment for advanced HCC. Despite its use, the overall survival extension for these patients remains limited due to the drug's ineffectiveness, and the mechanism behind advanced HCC's resistance to sorafenib remains elusive. TCGA analysis of HCC patient cohorts reveals elevated YBX1 expression in tumors compared to normal tissues. This heightened expression correlates with disease progression, metastasis, and poor survival rates among HCC patients. YBX1, a transcription factor known for regulating drug resistance in various cancers, particularly in colorectal and breast cancers, piqued our interest in investigating its potential involvement in sorafenib resistance within HCC. Employing MTT assays, we determined the IC50 values of sorafenib at different time points (24 and 48 hrs) on HCC cell lines obtained from ATCC. Overexpression of YBX1 resulted in increased cell survival and raised IC50 values for sorafenib at both time points, supporting the hypothesis that underscores YBX1's pivotal role in promoting sorafenib resistance in advanced HCC. To delve deeper, our lab developed puromycin-stable GFP-expressing cell lines for both YBX1 overexpression and knockdown, facilitating further mechanistic investigations. Additionally, we are progressing in establishing sorafenib-resistant HCC cell lines and conducting ongoing protein and RNA analyses on these resistant cells. Understanding the efficacy of sorafenib in treating advanced HCC and unraveling the signaling pathways associated with YBX1-induced drug resistance holds promise in significantly improving the prognosis for individuals battling this malignancy.
Academic/Professional Position
Graduate Student
Mentor/PI Department
Immunology and Microbiology
Recommended Citation
Kwabiah, Dennis; Doxtater, Kyle; Abuchard, Yamile; Leslie, Sophia; Bracho, Ricardo Pequeno; Hussain, Shaibir; and Tripathi, Manish K., "Unraveling Sorafenib Resistance in Hepatocellular Carcinoma: Exploring Key Facets" (2024). Research Symposium. 69.
https://scholarworks.utrgv.edu/somrs/2024/posters/69
Included in
Medical Biochemistry Commons, Medical Cell Biology Commons, Medical Molecular Biology Commons, Oncology Commons
Unraveling Sorafenib Resistance in Hepatocellular Carcinoma: Exploring Key Facets
Hepatocellular carcinoma (HCC) stands as the prevalent form of primary liver cancer worldwide, diagnosing over half a million new cases annually. Surgical interventions like hepatectomy and liver transplantation offer a potential cure for early-stage HCC. However, the prognosis for advanced stages remains grim due to drug resistance, particularly with high refractoriness rates. Sorafenib, a tyrosine kinase inhibitor, is an approved treatment for advanced HCC. Despite its use, the overall survival extension for these patients remains limited due to the drug's ineffectiveness, and the mechanism behind advanced HCC's resistance to sorafenib remains elusive. TCGA analysis of HCC patient cohorts reveals elevated YBX1 expression in tumors compared to normal tissues. This heightened expression correlates with disease progression, metastasis, and poor survival rates among HCC patients. YBX1, a transcription factor known for regulating drug resistance in various cancers, particularly in colorectal and breast cancers, piqued our interest in investigating its potential involvement in sorafenib resistance within HCC. Employing MTT assays, we determined the IC50 values of sorafenib at different time points (24 and 48 hrs) on HCC cell lines obtained from ATCC. Overexpression of YBX1 resulted in increased cell survival and raised IC50 values for sorafenib at both time points, supporting the hypothesis that underscores YBX1's pivotal role in promoting sorafenib resistance in advanced HCC. To delve deeper, our lab developed puromycin-stable GFP-expressing cell lines for both YBX1 overexpression and knockdown, facilitating further mechanistic investigations. Additionally, we are progressing in establishing sorafenib-resistant HCC cell lines and conducting ongoing protein and RNA analyses on these resistant cells. Understanding the efficacy of sorafenib in treating advanced HCC and unraveling the signaling pathways associated with YBX1-induced drug resistance holds promise in significantly improving the prognosis for individuals battling this malignancy.