Discovering protein biomarkers in patient blood is ideal due to easy access to the sample. However, the high dilution of protein biomarkers released into the circulation from disease-targeted organs or tumors makes it challenging to measure relevant protein biomarkers in blood (serum or plasma) with the required sensitivity. Consequently, this has hindered protein biomarker discovery in serum or plasma. To overcome this constraint, biomarker discovery can be directly performed in tissue biopsies where expression levels are highest, and biomarkers can be later translated into higher sensitivity technologies in plasma, as described in the following section. There are several antibodybased technologies that can be used for biomarker discovery and validation. One of the most attractive options is based on highly multiplexed protein immunoassays. These immunoassays use antibodies specific to multiple biomarkers, allowing for the simultaneous measurement of numerous proteins in a single sample. These assays are sensitive, precise, and can measure protein biomarkers in various sample types, including serum, plasma, and tissue. Therefore, they are widely used in biomarker discovery and validation, allowing for the identification of potential diagnostic and therapeutic targets for various diseases, including cancer.