Page 19 - Hormel Report 2023

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inhibitor of PRPK that almost totally prevents solar UV-induced skin cancer development and recurrence. The inhibitor is a repurposed FDA- approved drug, rocuronium bromide. This drug is currently used as a muscle relaxing agent during surgery. We have completed some preliminary testing of this drug and found it to be very stable and totally nontoxic when the formulation is applied to the skin. This drug is currently undergoing pre-IND (Investigational New Drug) testing that is required for moving it forward into first in human clinical trials.
ORCID iD:
https://orcid.org/0000-0002-7432-082X
PUBLICATION HIGHLIGHTS:
• 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. CiteScore: 16.9
• Wang, Q., Bode, A. M., & Zhang, T. (2023). Targeting CDK1 in cancer: mechanisms and implications. npj Precision Oncology, 7(1), 58.
• Ruiz, V. H., Encinas-Basurto, D., Sun, B., Eedara, B. B., Roh, E., Alarcon, N. O., Curiel-Lewandrowski, C., Bode, A. M., & Mansour, H. M. (2023). Innovative Rocuronium Bromide Topical Formulation for Targeted Skin Drug Delivery: Design, Comprehensive Characterization, In Vitro 2D/3D Human Cell Culture and Permeation. Int J Mol Sci, 24(10).
• Carbone, G., Nelson, K., Baumgartner, C., Bode, A. M., Takahashi, A., & Chefetz, I. (2023). Endometriosis: Cell Death and Cell Signaling Machinery. Endocrinology, 164(6).
• Li, Z., Tan, Y., Li, X., Quan, J., Bode, A. M., Cao, Y., & Luo, X. (2022). DHRS2 inhibits cell growth and metastasis in ovarian cancer by downregulation of CHKα to disrupt choline metabolism. Cell Death Dis, 13(10), 845.
• Hai, R., Yang, D., Zheng, F., Wang, W., Han, X., Bode, A. M., & Luo, X. (2022).
The emerging roles of HDACs and their therapeutic implications in cancer.
Eur J Pharmacol, 931, 175216.
EGFR
UV
P PRPK
Keratinocyte membrane
immune cell response DNA damage
genetic changes
PI3-K
P
AKT
P ERK1/2
PDL1
TOPK
P
PDL-1
CD70
Inflammatory cytokines
STATs NF-kB AP-1 CREB
CD70
DNA damage/apoptosis
Keratinocyte membrane
Immune cell membrane
CD27 PD1
Simplified pathway depicting solar UV-induced activation of the TOPK/PRPK pathway and its effects on signaling in keratinocytes and immune cells.
suppression induced by solar UV. The lack of com- plete understanding might be due, to some extent,
to the lack of comprehensive integrative research studies that allow combinatorial targeting of the various key steps in the early and overall process of solar UV-induced skin carcinogenesis. We discovered 2 new promising protein kinase targets for preventing solar UV-induced skin cancer. The T-LAK cell-originated protein kinase (TOPK) is involved in tumor develop- ment, growth, apoptosis, and inflammation. TOPK
is highly expressed in NMSCs and melanoma.
We also found that p53-related protein kinase (PRPK), downstream of TOPK, is a crucial player in skin cancer development. We are examining the role of TOPK and PRPK in solar UV-induced skin cancer and testing the effectiveness of TOPK and PRPK inhibitors in preventing and treating solar UV-induced skin cancer. We have identified a highly effective