Genetic Therapy for Pancreatic Cancer: Is it the Future.
Although surgery is still the only curative therapy for pancreatic cancer, oncological therapies have started to be more and
more promising.
We firstly have to consider two important points. The first one is that surgery for pancreatic cancer is complex and risky:
perioperative mortality is 4-18% and major complications occur in more than 40% of cases. Moreover, only 15-20% of patients have a resectable tumour at the first diagnosis.
Furthermore, disease’s recurrence following operation is very high because of local invasion and micrometastases at the time of surgery. The second point is that the first chemotherapies for pancreatic cancer are not specific for pancreatic tumours and have been provided only a little impact on overall survive. To obtain more efficient chemotherapies, we have to comprehend the molecular biology of pancreatic cancer.
Recent articles have shown the principal gene mutations in pancreatic tumoural cells. The earlier events involve telomere
shortening, KRAS mutation and p16 loss; the later ones are mainly P53 loss, SMAD4 loss and BRCA2 mutations.
Pancreatic cancer also overexpress multiple mitogenetic growth factors and their ligands i.e. epidermal growth factor receptor. Other studies have underlined the importance of the developmental program of epithelial to mesenchymal transition especially for metastatisation.
This process is regulated by inducing transcription factors as TGF-beta, Wnt/beta-catenin, Notch signaling, Snail transcription factors, zinc-finger-enhancer binding protein family and basic helix loop helix transcription factors.
Recently, the role of cancer stem cells has been found to be responsible for tumour recurrence and metastases. Notch, Hedgehog and Wnt/beta-catenin signaling pathways have a role in maintaining stem cells’ line in pancreatic cancer.
Pancreas Open J. 2016; 2(1): e1-e2. doi: 10.17140/POJ-2-e005
