P1, N=63, Completed, Thomas Helleday Foundation | N=100 --> 63 | Trial completion date: Dec 2025 --> Dec 2024 | Trial primary completion date: Dec 2025 --> Dec 2024 | Recruiting --> Completed

P1, N=9, Recruiting, Thomas Helleday Foundation | Trial completion date: Jan 2026 --> Dec 2026 | Trial primary completion date: Jan 2026 --> Dec 2026

Here, we summarize all available research on MTH1 mRNA, protein and its enzymatic activity in clinical samples across various cancer types, identifying a subset of cancers where MTH1 plays an important role. This is particularly evident in cancers characterized by high metabolic activity and oxygen-rich environments, such as hepatocellular carcinoma, renal cell carcinoma, or non-small cell lung adenocarcinoma.

Our research emphasises the role of NUDT1 in modulating the intestinal microbiota and intestinal mucosal barrier in UC, indicating that targeting NUDT1 during intestinal mucosal inflammation could serve as a promising therapeutic strategy for UC.

Conversely, KRAS depletion or its inhibition by AMG-510 (sotorasib) decreased MTH1 in KRASG12C-addicted LUAD cells...Our studies suggest that despite loss of KRAS dependency, LUAD cells retain the requirement for high MTH1 8-oxodGTPase activity due to redox vulnerabilities associated with AKT signaling. Thus, MTH1 may serve as a novel orthogonal vulnerability in LUAD that has lost KRAS addiction.

MTH1 inhibition reduced proliferation and promoted apoptosis of T cells in vitro. In vivo, TH1579 dampened the type 2 associated immune response in a murine model. These findings suggest that MTH1 could serve as a novel target to treat allergic airway inflammation.

Meanwhile, the released functional nucleic acid G3139 downregulated the expression of Bcl-2, and accelerated the apoptosis of tumor cells. In conclusion, the HTCG@TA demonstrated significant effect in oxidative damage amplification and tumor inhibition both in vitro and in vivo, which has provided a new outlook for the clinical application of chemo-dynamic tumor treatment and synergistic gene therapy with self-delivery nanoplatforms.

P1, N=100, Recruiting, Thomas Helleday Foundation | N=35 --> 100 | Trial completion date: Jun 2022 --> Dec 2025 | Trial primary completion date: Dec 2021 --> Dec 2025

P1, N=9, Recruiting, Thomas Helleday Foundation | Trial completion date: Jun 2022 --> Jan 2026 | Trial primary completion date: Dec 2021 --> Jan 2026

An in vivo experiment in a syngeneic mouse melanoma model showed that TH1579 treatment significantly increased the efficacy of atezolizumab, an anti-PD-L1 antibody, compared to vehicle or atezolizumab monotherapy. Furthermore, TH1579 exhibited immune-modulatory properties, elevating cytokines such as IFN-β and chemokines including CCL5 and CXCL10, in a cGAS-STING pathway-dependent manner. In conclusion, TH1579 has the potential to improve ICI treatment by modulating immune checkpoint-related proteins and pathways.

MA-24 possesses a broad spectrum of breast cancer cytotoxicity and offered valuable insights for overcoming the challenges of chemotherapy-related toxicity, which holds great potential for the further development MA-24 as an anti-cancer drug.

Combined MTH1 and PD-L1 inhibition holds promise for the successful clinical management of mesothelioma.