Krey Daniel

Targeting the NF-kB pathway in cancer pathogenesis

Started Oct. 26, 2021

Abstract or project description

The cyclooxygenase-2 (COX-2) enzyme has been shown to play a major role in aiding the development of cancer, as it catalyzes certain prostaglandins, setting off a pathway facilitating numerous cancerous processes. Current therapies targeting COX-2, such as the use of NSAIDS and COX-2 inhibitors have been shown to cause numerous adverse side effects. However, expression of COX-2 is regulated by the NF-kB signal transduction pathway. Through a literature review, I would like to explore the possibilities of regulating this pathway in order to decrease COX-2 levels and thus aid in battling the development of cancer, while also avoiding the negative side effects caused by current treatment methods. We will discuss various treatments modulating activity of members of the pathway, such as small molecule treatments, nucleic acid therapies, and antibody-based therapies, for their benefits and drawbacks. Small-molecule therapies utilize tiny molecules to target specific proteins in the pathway. Potential targets include subunits of NF-kB such as c-Rel, signaling molecules and receptors such as those in the TNFRSF family, proteins involved in degradation called proteasomes, and nuclear transport molecules, those which travel between the cytoplasm and the nucleus. Nucleic acid therapy is a rising field which utilizes RNA and DNA sequences to modify the transcription and translation of target genes. Some avenues of nucleic acid therapy include antisense oligonucleotides (ASOs), microRNAs (miRNAs) and miRNA mimics, and small interfering RNAs (siRNAs). Finally, antibody-based therapies utilize antibodies to target cancer cells and direct immune responses against them. Finally, we will discuss the potential of these treatments and what promise they show for future studies to move forward with.