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SUMO modification is emerging as an important post-translational control of cellular events. Our study primarily focused on the molecular mechanisms as to how protein sumoylation is regulated and what consequence of a protein is sumoylated in cancer giving that sumoylation levels are elevated in several types of human cancer. We have demonstrated several other modifications such as phosphorylation and acetylation could control protein sumoylation. Since SUMO pathway has been considered as a non-oncogene addiction in cancer, targeting SUMO machinery and/or sumoylated substrates could not only understand the underlying mechanism of sumoylation associated with cancer but also increase the repertoire of druggable targets against cancer. This talk will cover the functional significances of cancer-associated sumoylated factors as well as to develop therapeutic agents in targeting SUMO conjugation and binding in cancer.