Significance of P2RY2 in NSCLC

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related deaths worldwide. In 2022, around 2.5 million new cases were diagnosed, resulting in approximately 1.8 million fatalities. There are two main types of lung cancer: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for around 85% of lung cancer cases and is a leading cause of cancer death due to its aggressive behaviour and complex tumourimmune dynamics. The five-year survival rate for patients with NSCLC at all stages is around 28%, falling to 9% for those with distant metastatic disease. While targeted therapy has produced significant benefits for certain molecular subtypes of NSCLC, traditional chemotherapy typically offers only temporary relief and remains the primary treatment option for most patients. Consequently, there is a significant unmet need for therapies that can extend survival without compromising quality of life. In recent years, the role of the immune system in cancer development and progression has been increasingly recognised, with a corresponding focus on using immunotherapy in clinical practice and regulatory approvals of immunotherapy. While NSCLC has always been seen as a non-immunogenic disease, new evidence has shown that the lack of an effective immune response is often due to specific, active immune-evasive mechanisms. If these mechanisms are understood, they can be overcome therapeutically with significant clinical efficacy. This potential has therefore become a primary area of clinical interest. The P2Y2 purinergic receptor is widely expressed in various immune cell types, suggesting that it may play a regulatory role in the immune microenvironment. While P2RY2 has been associated with promoting tumour growth in several types of cancer, its specific function in NSCLC remains poorly understood. Our study aims to elucidate the tumor-promoting role of P2RY2 in NSCLC. Additionally, we will evaluate the therapeutic effects of the receptor in preclinical models. Lung cancer is not sex-specific. However, women generally have a lower lifetime risk of developing lung cancer and a lower mortality rate than men. This difference is likely due to environmental factors and biological differences. Additionally, there are differences in therapeutic response between the sexes. Therefore, our study will include both genders. Our research offers new insights into tumor-immune interactions and immunotherapy strategies that may provide new approaches to combating NSCLC.