The role of endolysosomal cation channels, particularly TPC2, in cancer prognosis, and diagnosis: novel therapeutic targets for cancer

The role of endolysosomal cation channels, particularly TPC2, in cancer prognosis, and diagnosis: novel therapeutic targets for cancer

Lay summary

Cancer is a major public health problem and one of the leading causes of death worldwide. Cancer biomarkers have emerged as clinical tools that can enhance the efficiency of detection and guide the treatment of cancer patients by providing personalised therapy and information about expected cancer outcomes. Recently, there is increasing evidence that links endolysosomal cation channels and cancer, particularly two-pore channel 2 (TPC2), revealing the potential applications of TPC2 as a biomarker in the definition of tumour types, susceptibility, prognosis, response and cancer outcomes.

The mechanisms that underpin the role of TPC2 in various fundamental processes of oncogenesis, in different types of cancer and at different stages of tumour development are not fully understood. We aim to investigate the association between genetic mutations in endolysosomal cation channel genes and cancer. Furthermore, we will examine the role of the identified genetic mutations in cancer. The findings of this study might have significant implications for future practice by improving diagnosis, prognosis and treatment in cancer patients, as well as providing insights to better understand the pathogenesis of cancer.

Scope extension:

Aim 1: To characterize effects of genetic variants within but not limited to TPC1-2, TRPML1-3, P2X4, and other genes involved in Ca2+ signalling, on cancer.

Aim 2 will develop in vitro models to examine the role of the significant mutations in endolysosomal cation channels during tumour formation (involving neoangiogenesis) and cancer cell migration.

Aim 3 will validate the clinical utility of genetic variants in endolysosomal cation channels as diagnostic or prognostic biomarkers in an independent cohort.

Aim 4 will investigate the association between exposure to solarium or sunlamp and melanoma risk in carriers of TPCN2 rs35264875: TA or TT vs AA.