Proteomic technologies for profiling cell-membrane/secretome interactions in brain metastatic cancer progression.

. The ability of cancer cells to disseminate from the primary tumor and form metastatic lesions frequently leads to fatal outcomes. Recently, however, it has been recognized that this process is driven by complex interactions between the cancer and the neighboring cells, and, overall, made possible by a supportive tumor microenvironment. The emergence of high-throughput technologies is expected to bring much needed clarity to unraveling the players and intricate communication pathways that promote metastatic progression. In this report, the impact of mass spectrometry and proteomic technologies on deciphering the cross-talk between cancer and tumor microenvironment cells is discussed. Focus is placed on the role of cell-membrane and secretome proteins as the main enablers of this cross-talk, and on the challenges presented by metastatic tumors that evolve in the brain. Future prospects are assessed in the context of recent biology, technology, and data analysis breakthroughs. Advancements in high-throughput proteomic technologies, complemented by the exciting potential of new disease model systems and data processing abilities of artificial intelligence, are expected to bring groundbreaking progress in deciphering the fundamental biological mechanisms that support cancer behavior and metastatic development, revealing novel therapeutic targets, and guiding innovative intervention approaches.