TYMP (Thymidine Phosphorylase)

Though POI is not a well-established feature of MTDPS1, mutations in other genes linked with mitochondrial function are known to be associated with POI and we postulate that this is an endocrine manifestation of MTDPS1. Genetic assessment should be considered in unexplained POI, particularly if associated with other clinical features/consanguinity.

The thoroughly described pathophysiological basis of TYMP activity corresponds with the pathological mechanisms of numerous disorders. Modulating its actions may serve as an attractive novel therapeutic target in: the COVID-19-associated thrombotic complications, resistance to myocardial infarction-associated cardiomyocyte damage, aneurysm development, atherosclerosis progression, and neurological diseases, including stroke.

TYMP expression positively correlated with both CEBPB and GDF15 levels in public datasets. Collectively, our findings define a CEBPB/TYMP/GDF15 signaling axis that fosters BC progression and cisplatin resistance and highlight TYMP as a novel prognostic biomarker and potential therapeutic target, with TAS-102 offering a promising strategy for overcoming cisplatin resistance.

TYMP was highly associated with immune checkpoint CD276 and was an macrophage biomarker in many cancers. This study will reveal TYMP's roles in pan-cancer and its potential as a novel therapeutic target, especially KIRC.

The combination of TYMP and Six1 is a good predictive and prognostic biomarker for GC. This combination enhances the expression of VEGFc, facilitates the invasion of GC cells, and may be linked to inhibitory immune cells and the tumor immune microenvironment.

Interestingly, while TYMP can drive tumor growth, certain concentrations of TYMP also enhance the cytotoxic effects of chemotherapy drugs such as 5-fluorouracil (5-FU)...Ongoing research on TYMP could deepen our understanding of human physiology and the pathogenesis of cancer and open new avenues for therapeutic interventions. This article provides a comprehensive review of TYMP's structure, physiological functions, and its role in tumorigenesis and anti-tumor therapy.

P=N/A, N=20, Recruiting, Columbia University | N=10 --> 20 | Trial completion date: Mar 2025 --> Dec 2026 | Trial primary completion date: Mar 2025 --> Dec 2026

Platelets of WT mice treated with TPI or platelets of Tymp-/- mice exhibited the adverse results. Our study illustrates the vital role of TYMP in promoting RA inflammation and platelet activation, suggesting that TYMP may be a potential therapeutic target for RA.

In addition, we find that TBK1 inhibitors can act synergistically with AKRB10 and TYMP inhibitors to reduce cell viability. These findings raise the possibility that combining these inhibitors might be beneficial in combating cancers that show elevated levels of TBK1.

Hepatic TYMP expression level may serve as a promising imaging biomarker for differential diagnosis of SS and MASH. SPECT imaging using [123I]IIMU potentially provides a novel noninvasive diagnostic method to differentiate MASH and SS.

Trifluridine combined with tipiracil, a specific thymidine phosphorylase inhibitor, in TAS-102 has recently emerged as a potential alternative in the face of primary or secondary chemoresistance to 5-fluorouracil. To study the importance of macrophages in chemoresistance to trifluridine, we developed a humanized mouse model with tumor-implanted human macrophages and demonstrated their important role in treatment resistance to pyrimidine analogs. Additionally, our findings revealed that macrophages represent a significant source of thymidine phosphorylase expression, comprising over 40% of the expressing cells, in human colorectal cancer, thereby contributing to chemoresistance.

P=N/A, N=10, Recruiting, Columbia University | Trial completion date: Aug 2024 --> Mar 2025 | Trial primary completion date: Aug 2024 --> Mar 2025