The present invention relates to a method for preventing or treating a cancer disease by targeting the epigenetic factor Chromodomain on Y-like 2 (CDYL2). The inventors found that CDYL2 is commonly over-expressed in cancer and high CDYL2 levels correlate with poor prognosis in a number of cancer types even in drug resistant cancer. CDYL2 upregulation in a breast cancer cell line induced migration, invasion, stem-like phenotypes, as well as an epithelial-to-mesenchymal transition (EMT). Due to the importance of EMT and stemness in therapeutic resistance and relapse in cancer, the inventors propose that CDYL2 inhibition will also be beneficial to the treatment of such cancers. Furthermore RNAi inhibition of CDYL2 diminished these same EMT-associated processes in the mesenchymal-like breast cancer cell line. Finally ablating the expression of CDYL2 with RNAi 1) stimulates the expression of genes associated with an anti-tumor immune response (such as gene involved in interferon response) and 2) inhibits lung tumorigenesis in a preclinical model (mouse injected with the triple negative MDA-MB-231 cell line). These results show that CDYL2 as a strong candidate proto-oncogene and therapeutic target in cancer and also contributes to the anti-tumoral immune response escape.