Also, the deep-tumor delivery of Gem in pancreatic tumors is compromised due to desmoplasia 5 comprising excessive accumulation of proteinaceous material with cytokines and stellate cells which prevents deep diffusion of the drugs at the center of the tumor site. However, Gem has a short plasma half-life (< 20 min) due to the rapid conversion to the inactive metabolite (2′,2′-difluorouridine) by cytidine deaminase which severely limits its efficacy 4. Gemcitabine (Gem) is currently the leading therapeutic for pancreatic cancer therapy, administered as monotherapy or in combination with other drugs in order to mitigate the problem of drug resistance development and to augment the therapeutic outcome 3. The incidence of pancreatic cancer is almost equal with the mortality rate, with less than 5% 5-year survival 1, 2.
Pancreatic cancer is one the most aggressive human malignancies, with an extremely dismal prognosis due to absence of symptoms and lack of reliable screening tests for early diagnosis.