The role of TRPA1 in lung cancer

Lung cancer is the leading cause of cancer related death worldwide and is typically categorised as either small cell lung carcinoma (SCLC) or non-small cell lung carcinoma (NSCLC). SCLC accounts for 15% of all lung cancer diagnoses while NSCLC accounts for 85%. In NSCLC, 70% of patients are at an advanced stage at diagnosis, which limits surgical options. A key management challenge is the high levels of drug resistance that occur over time, which impact treatment strategies. Transient receptor potential ankyrin-1 (TRPA1) is a nonselective ion channel with a high permeability for calcium which is involved in numerous physiological functions, including thermoregulation, nociception, phagocytosis, cell motility and inflammatory pain sensation. The TRPA1 receptor is present throughout the respiratory tract and its role in inflammatory conditions such as asthma and chronic obstructive pulmonary disease (COPD) have been well established. TRPA1 has been implicated in the pathogenesis of a variety of cancers, and interest in its role in the oncology setting is expanding. It has been implicated in the development of prostate cancer, breast cancer, oral squamous cell carcinoma, colorectal carcinoma and pancreatic ductal adenocarcinoma. However, the role of TRPA1 in lung cancer has yet to be fully investigated. In silico studies have suggested that TRPA1 messenger ribonucleic acid (mRNA) is upregulated in NSCLC, both in lung squamous cell carcinoma (SCC) lung adenocarcinoma (LUAD). Moreover, TRPA1 expression showed a positive correlation with increased lung cancer stages and risk of metastasis. Potential involvement in SCLC and SCC development have been demonstrated by a number of studies, however information regarding the role of TRPA1 in LUAD is scant. This represents an active research gap which should be addressed, given the role that TRPA1 appears to play in the inflammatory lung milieu and other malignancies. In this review, we outline the current knowledge surrounding the biological roles of TRPA1 in the lung, summarize the existing drug strategies to target this receptor, and discuss the potential for its targeting either as an anticancer strategy or alternatively for its use in pain management for patients suffering from lung cancer.