The Fhit protein: an opportunity to overcome chemoresistance

Since the very first moment of its discovery in 1996 [1], the FHIT (Fragile Histidine Triad) gene product appeared as a very intriguing molecule to be investigated in the pathogenesis of cancer. In fact, FHIT encompasses the most common fragile site in human [2], whose genetic alterations, leading to the loss of FHIT expression, have been reported in the majority of human cancers [3]. Other than genetic lesions, FHIT expression in both solid and hematopoietic malignancies is also impaired by its promoter hypermethylation [4, 5], making Fhit protein virtually completely lost in tumors. Moreover, several reports have intriguingly pointed to Fhit loss as a very early event in epithelial tumorigenesis (presumably, the earliest event in smoking-related lung cancer) [3].