Ahmadzada et al. Biomarkers in mesothelioma who are candidates for surgery undergo either extra-pleural pneumonectomy (EPP), which involves macroscopic removal of the diseased pleura together with the lung, pericardium and hemi-diaphragm, or a radical pleurectomy/decortication (P/D)(1). Surgical management is typically combined with chemotherapy and/or radiotherapy as surgical microscopic clearance is difficult to achieve (1, 2). However, most patients are not suitable candidates for surgery, making systemic chemotherapy the mainstay treatment for most patients (1). Currently, there are only two Food and Drug Administration (FDA)-approved chemotherapeutic drugs for MPM: cisplatin and pemetrexed (3). They have been used as standard of care in MPM for over a decade. No second-line treatments for MPM have yet been approved for standard of care treatment. Combining cytotoxics with an anti-vascular endothelial growth factor (VEGFA) approach has shown promise. The addition of bevacizumab (MAPS study)(5) or nintedanib (LUME-Meso study)(6) to chemotherapy has been investigated with some success in clinical trials. Currently, there is intense interest in the use of immunotherapy in MPM due to the promising results of KEYNOTE-028 using single agent pembrolizumab, a programmed death protein 1 (PD-1) antibody (7). PD-1 is expressed on effector lymphocytes, while its natural ligands, PD-L1 and PD-L2, are expressed on tumour cells or in the surrounding microenvironment (1). The PD-1/PD-L1 pathway downregulates T-cell function, which can facilitate tumour rejection by the immune response (1, 3). These receptors can be targeted by monoclonal antibodies that block PD-1/PD-L1 pathways. Currently there are several international trials using the PD-1/PD-L1 approach, typically in combination with chemotherapy [pembrolizumab and chemotherapy in a Canadian trial (NCT02784171) and durvalumab and chemotherapy (DREAM; ACTRN12616001170415)] or with other immunotherapy agents [nivolumab and ipilimumab (CheckMate743; NCT02899299)]. It is clear that there are several clinical challenges with MPM. There is an urgent and unmet need for noninvasive biomarkers that can assist in early diagnosis, better define prognosis and predict patient responses to available treatments. A biomarker is a characteristic that can be measured and that gives an indication of the biological state of the patient. Diagnostic biomarkers can differentiate the disease of interest from other diseases or normal state; prognostic biomarkers inform us about the pace of disease progression and outcome regardless of treatment; and predictive biomarkers tell us whether a patient will benefit from a particular treatment. An ideal biomarker for MPM should be inexpensive, reproducible, easy to obtain and easily sampled with a minimally invasive technique, making blood-based tests prime for investigation. The search for mesothelioma biomarkers has been ongoing for the last 30 years. So far, three blood-based biomarkers have been extensively investigated for MPM for their diagnostic potential: soluble mesothelin, osteopontin and fibulin-3, as discussed in the review by Sun et al.(4). Soluble mesothelin, also known as soluble mesothelinrelated peptide (SMRP), is a glycoprotein encoded by the MSLN gene. It is expressed on the surface of normal mesothelial cells in limited amounts and overexpressed by tumour cells in most MPM tumours and other cancers (1, 2). The regulation of mesothelin expression is not fully understood, however it has been observed that mesothelin can be shed from the cell surface and can be detected in the blood (2 …