Table 1 Clinically validated targeted proteomics assays with applications in oncology
From: Recent developments in mass-spectrometry-based targeted proteomics of clinical cancer biomarkers
Marker | Matrix | Clinical utility | Advantage of targeted LC–MS/MS assay | Methodology of targeted LC–MS/MS assay | Reference |
|---|---|---|---|---|---|
Thyroglobulin | Serum | Monitoring of patients with differentiated thyroid cancers after thyroidectomy and radioactive iodine ablation | Quantification not impacted by anti-thyroglobulin antibodies, which hinder accurate thyroglobulin quantification via immunoassay | Immunoaffinity-based peptide enrichment | Shuford et al. [19] |
Chromogranin A | Serum | Monitoring of patients with carcinoid tumors, support diagnosis of carcinoid tumors and other neuroendocrine tumors | Wider dynamic range (quantification over 4 orders of magnitude); increased throughput per batch versus a commercially available immunoassay | Protein enrichment via mixed-mode anion exchange solid-phase extraction | Weber et al. [20] |
PTH-related protein | Serum | Diagnosis and management of patients suspected of hypercalcemia of malignancy | Improved analytical sensitivity over commercially available radioimmunoassay; potential for improved diagnosis of PTHrp as a cause of hypercalcemia of malignancy; avoids need to use radioactive tracers used in the established radioimmunoassays | Immunoaffinity-based protein enrichment followed by on-bead digestion | Kushnir and Rockwood [21] |
Monoclonal antibody therapies (bevacizumab, evolocumab, nivolumab, pembrolizumab, and trastuzumab) | Serum | Therapeutic drug monitoring, dose optimization | Efficient and reproducible method widely applicable to IgG-based monoclonal antibody therapeutics in plasma | Immunoaffinity-based protein enrichment (IgG) followed by on-bead digestion | Chiu et al. [22] |
Rituximab | Serum | Therapeutic drug monitoring | Precise and accurate method with high inter-lab concordance | Immunoaffinity-based protein enrichment (IgG) or trichloroacetic acid/isopropanol-based albumin depletion | Millet et al. [23] |
Cetuximab | Serum | Therapeutic drug monitoring | Quantification not impacted by endogenous interferences that may impact ELISA measurements | High pH peptide fractionation No protein or peptide enrichment/fractionation | Becher et al. [24] Shibata et al. [25] |