GAPDH and mitochondrial dynamics regulation: novel insights to treat PDAC having TP53 mutant gene.

Pancreatic adenocarcinoma (PDAC) is one of the most aggressive and devastating human malignancies. Late diagnosis is due to an absence of specific symptoms at initial stages. In about 70% of PDACs, the tumor suppressor gene TP53 has missense mutations generally resulting in conformational changes of mutantp53 (mutp53) proteins. This represents important event in the carcinogenesis process, not only through loss of p53 wild-type activity, but also through gain of specific mutp53 functions. In contrast to the tumor suppressive roles of wild-type p53, mutp53 proteins support cancer progression by enhancing the ability of cancer cells to invade and metastasize, to confer chemo-resistance, and to stimulate genomic instability. We focused our attention on novel molecular mechanisms by which mutp53 proteins play their oncogenic roles promoting cancer cell proliferation and chemoresistance. The need to find a better strategy by identifying novel mechanisms involving mutp53 in PDAC is thereby tremendously increasing.