Page 17 - Hormel Institute Annual Report 2021-22

and carcinogenesis. We are also examining the effi- cacy of TOPK/PRPK inhibitor(s) in preventing solar UV-induced skin carcinogenesis. With the Center for Translational Medicine, UMN, we are conducting IND-enabling pre-clinical studies in preparation to move a PRPK inhibitor into clinical trials.
A second project mostly led by Dr. Tianshun Zhang focuses on mechanisms of esophageal cancer development. Esophageal cancer is a major health issue worldwide with increasing incidence and persistently high mortality, mainly because of its diagnosis at advanced stages. Gastro-esophageal reflux disease (GERD) causes chronic injury to
the esophagus, referred to as Barrett’s esophagus (BE), which is the pre-neoplastic lesion preceding esophageal adenocarcinoma (EAC) incidence. Despite surgery combined with chemotherapy and radiotherapy, the overall 5-year survival rate of EAC patients is less than 20%. Early detection or preven- tion of progression to EAC is critical for improved
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outcomes. Prostaglandins (PGs) are implicated
in cancer development. Little is known about the profiles of circulating PG biosynthesis in GERD or BE. Our preliminary analysis indicated that plasma sam- ples from patients with GERD, BE, or EAC had much higher circulating levels of thromboxane A2 (TXA2) compared to normal individuals. In a patient trial with Mayo Clinic, we found that aspirin could prevent the elevation of TXA2.
A third project focuses on targeting Aurora B kinase and B-RAF to overcome drug resistance in melanoma.
Molecular signaling pathways involved in solar UV-induced skin cancer development
Recent Publications:
• Wang, Q., Morris, R. J., Bode, A. M., & Zhang, T. (2022). Prostaglandin Pathways: Opportunities for Cancer Prevention and Therapy. Cancer Research, 82(6), 949-965. (Featured article)
• Tang, M., Dong, X., Xiao, L., Tan, Z., Luo, X., Yang, L., Li, W., Shi, F., Li, Y., Zhao, L., Liu, N., Du, Q., Xie, L., Hu, J., Weng, X., Fan, J., Zhou, J., Gao, Q., Wu, W., Zhang, X., Liao, W., Bode, A. M., & Cao, Y. (2022). CPT1A-mediated fatty acid oxidation promotes cell proliferation via nucleoside metabolism in nasopharyngeal carcinoma. Cell Death Dis, 13(4), 331.
• Zhao, L., Deng, X., Li, Y., Hu, J., Xie, L., Shi, F., Tang, M., Bode, A. M., Zhang, X., Liao, W., & Cao, Y. (2021). Conformational change of adenine nucleotide translocase-1 mediates cisplatin resistance induced by EBV-LMP1. EMBO Mol Med, 13(12), e14072.
• Xie, L., Zhou, T., Xie, Y., Bode, A. M., & Cao, Y. (2021). Mitochondria-Shaping Proteins and Chemotherapy. Front Oncol, 11, 769036.
• Quan, J., Bode, A. M., & Luo, X. (2021). ACSL family: The regulatory mechanisms and therapeutic implications in cancer. Eur J Pharmacol, 909, 174397.