Breast cancer is the most prevalent cancer type in women and one of the most common death causes in women worldwide. In the last decades, breast tumors have been classified into 3-4 subtypes, in order to assign the appropriate treatment modality and to determine patient prognosis. However, in many of the cases, patient do not respond to these treatments, or develop resistance and tumor relapse. One of the underlying causes of this resistance is the heterogeneity of the tumors. It is now recognized that most tumors are not actually composed of a single subtype, but are rather a heterogeneous mass of cells, of different clones, each one with its distinct characteristics. These distinct populations are affected by their mutational profiles that evolved with tumor development, and by the microenvironment of healthy cells adjacent to the cancer cells. We hypothesized that characterization of the various clones within single tumors will highlight the key regulators of tumor development. This study aimed to understand tumor heterogeneity in breast cancer, using state of the art proteomics technologies. Mass spectrometry-based proteomics monitors the global profiles of protein changes. Determination of protein levels reflects the cellular phenotype much more closely than genomic approaches, and is therefore expected to reveal tumorigenic mechanisms that cannot be identified by other approaches. Identification of the key regulators of tumor aggressiveness, and their spatial distribution in breast tumors has the potential to translate into efficient drugs that overcome development of treatment resistance, and lead to durable treatment responses.
