Date of Award
12-17-2025
Document Type
Masters Project
Abstract
Metabolism was a major focus of cancer research 100 years ago, but its prevalence declined in the latter part of the twentieth century. In the last several decades, however, it has become clear that cancer cells frequently modify their metabolic programs to enable both their survival and rapid proliferation. Transaldolase (TA), an enzyme within the pentose phosphate pathway, contributes to these outcomes when its activity is increased, yet for a variety of reasons inhibition of the enzyme has remained comparatively understudied. Since TA flux enables nucleotide production and high levels of NADPH synthesis, aberrant, cancer-causing signaling pathways often increase expression of the enzyme or otherwise boost the flow of metabolites through its pathway branch. TA has also been found to take part in a synthetic lethality condition with the breast-cancer drug lapatinib, enabling the treatment to gain efficacy against otherwise drug-resistant cancer cells. TA’s neighboring enzyme on the same branch, transketolase (TK), whose reactions occur prior to and after TA’s reactions, also affects nucleotide and NADPH production, and unlike TA, drug-like inhibitors for TK have long been in existence. The recent development of a safer prodrug based on one such older TK inhibitor likely will impact developmental considerations of a TA inhibitor, as the effect of interfering with the latter’s reactions could prove somewhat redundant. Still, TA inhibition arguably will lead to distinct, potentially useful clinical effects on carcinogenesis compared to TK inhibition, reinforcing the rationale behind such research.
Recommended Citation
Baer, Daniel Scot, "The feasibility of transaldolase inhibitors as anti-cancer therapeutics" (2025). Chemistry and Biochemistry. 164.
https://ualaska.researchcommons.org/uaf_grad_chem_biochem/164
Handle
http://hdl.handle.net/11122/16326