New publications in peer-reviewed scientific journals support the potential for OXC-101 as a novel anti-cancer therapy

OXC-101 shows promise in enhancing the effectiveness of immune checkpoint inhibitors. The article published in Oncogenesis by Helleday laboratory, Karolinska Institute, and Oxcia team suggests that the mitotic MTH1 inhibitor OXC-101 (TH1579) has the potential to enhance the effectiveness of immune checkpoint inhibitors (ICI) in cancer treatment. This is achieved by influencing immune checkpoint-related proteins and pathways (1). The researchers discovered that treatment with OXC-101 leads to an increase in PD-L1 expression and inflammatory response in cancer cell lines. This finding may provide an explanation for the enhanced effectiveness of the combination of atezolizumab and OXC-101 in a syngeneic melanoma disease model.

 
OXC-101 has also been found to synergize with oxidative stress-inducing drugs in killing cervical cancer using various preclinical models. Professor Ba's team from Northeast Normal University in Changchun, China, recently reported this (2). These findings corroborate our prior research on the involvement of MTH1 and ROS in cancer treatment. They indicate that a combination of lower dosages of drugs that induce ROS along with mitotic MTH1 inhibitor could be a more targeted and safer approach for treating cervical cancer compared to chemotherapy.

MTH1, the specific protein that OXC-101 targets, has a crucial role in the susceptibility of cancer cells to metabolic changes produced by MYC. This study, conducted by Professor Quing from Wuhan University in China, was recently published in the scientific journal Nature Communications (3). The findings of this study are consistent with our prior research, which identified that tumours with amplified CMYC are highly responsive to therapy with OXC-101 (4). MYC is a group of regulatory genes and proto-oncogenes that control vital physiological processes related to cell division and cell survival. It is widely recognised to play a role in numerous types of cancer. The latest research authored by Ye et al. proposes a fundamental mechanism that explains this discovery. They argue that MYC coordinates the equilibrium between two metabolic pathways that work simultaneously: the MTH1 (NUDT1)-PLK1 nucleotide-sanitizing system and the ROS-NOX4 pathway. This coordination is crucial for the survival of tumour cells. Therefore, the inhibition or degradation of MTH1 in cancer that is hyperactivated by MYC can be particularly intriguing and lead to the identification of new treatment strategies in the clinic.

References

 1. Shen et al., Mitotic MTH1 inhibitor TH1579 induces PD-L1 expression and inflammatory response through the cGAS-STING pathway, Oncogene (2024)12:17, PMID:38796460 

2. Li et al., MTH1 inhibition synergizes with ROS-inducing agents to trigger cervical cancer cells undergoing parthanatos., Biochem Biophys Acta Mol Basis Dis. 2024 Jun; 1870(5):167190, PMID: 38657912

3. Ye et al., Therapeutic targeting nudix hydrolase 1 creates a MYC-driven metabolic vulnerability., Nature Communication., 2024 Mar 16:15(1):2377, PMID: 38493213

4. Henriksson et al., Overexpression c-Myc Sensitizes Cells to TH1579, a Mitotic Arrest and Oxidative DNA Damage Inducer, Biomolecules 2022 Nov 29;12(12):1777, PMID: 36551206

For more information contact:

Ulrika Warpman Berglund, CEO, Oxcia AB (publ)

Telephone: +46 (0) 73 270 9605
ulrika.warpmanberglund@oxcia.com

Briefly about Oxcia

Oxcia AB is a pioneer in oxidative DNA damage and DNA Damage Response (DDR - the processes the body uses to repair the damage that occurs to DNA) with a focus on developing new safe treatments for patients suffering from diseases caused by cancer or inflammation. Oxcia currently has two DDR drug candidates, both with the potential to become first-in-class drugs. OXC-101  is in early clinical development as novel cancer therapy. OXC-201  is developed against inflammatory and fibrosis-related diseases, such as pulmonary fibrosis and allergic asthma, and is in the preclinical phase.

More information about Oxcia is available at www.oxcia.com