Chemoresistance is a common mode of therapy failure for many cancers. Tumors develop resistance to chemotherapeutics through a variety of mechanisms, with proteins serving pivotal roles. Changes in protein conformations and interactions affect the cellular response to environmental conditions contributing to the development of new phenotypes. The ability to understand how protein interaction networks adapt to yield new function or alter phenotype is limited by the inability to determine structural and protein interaction changes on a proteomic scale. In this project we combine SILAC with PIR cross-linking technology to generate a quantitative protein interaction map of drug senstive and drug resistant HeLa cells.