The role of two-pore channel 2 in monocyte differentiation as a novel therapeutic target for cancer

The role of two-pore channel 2 in monocyte differentiation as a novel therapeutic target for cancer

Lay summary

Cancer is a major public health problem and one of the leading causes of death worldwide. According to Cancer Research UK, every four minutes, someone in the UK dies from cancer. The treatment options for cancer are surgery, radiation therapy, chemotherapy, immunotherapy, targeted therapy, hormone therapy, and stem cell transplants. Despite advances in the treatment of cancer, there is a lack of useful and specific biomarkers for diagnosis and prognosis.

Moreover, early detection and total cure remain elusive for most patients. Two-pore channel 2 (TPC2 or TPCN2) is a eukaryotic voltage-gated ion channel located in the lysosome. The release of Ca2+ from this channel is regulated by the second messengers nicotinic acid adenine dinucleotide phosphate (NAADP) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2).  TPC2 is overexpressed in monocytes. Monocytes are recruited to target tumor tissues in response to tumor-derived factors, leading to their further differentiation into macrophages. Tumor-associated macrophages play a role in tumor growth and metastasis. Several studies have shown strong association between increased TAM density and poor survival. Therefore, we will conduct a study to investigate the association between genetic mutations in TPC2, monocytes and macrophages, and cancer. Survival data will be collected from the patients' records and calculated as the time from the date of diagnosis to the date of death or the date of the final documented follow-up.

Furthermore, we will examine the role of the identified genetic mutations in TPC2, monocytes and macrophages, during tumour formation and cancer cell migration. The findings of this study might expand our scientific knowledge about these genetic variants and how to utilize them to optimize cancer prevention and therapy.