RESEARCH p G d

Resistance mechanisms remain a key challenge in the fight against cancer. Acquired drug resistance is of major clinical significance both for conventional and targeted therapies [1]. The first cause of therapeutic failure results from genetic alterations existing before treatment. Several researchers have evidenced the role of epigenetic changes [2,3] as well as the influence of the tumor microenvironment [4] on che-moresistance. One of the main characteristics of tumor microenvironment is the presence of hypoxic areas. Hyp-oxia is known to affect gene expression not only by regulat-ing transcription [5] but also by epigenetic changes [6]. Furthermore, hypoxia and the adaptive responses of cancer cells play an important role in cancer progression [5]. Tumor microenvironment also strongly modulates the sen-sitivity of cancer cells to therapies. Previous results from our group showed that hypoxia protects tumor cells from apop-tosis induced by several chemotherapeutic agents [7,8]. This protective effect has also been demonstrated by others, using other cell lines and other drugs [9,10] suggesting a * Correspondence