Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors with a 5-year survival rate of less than 5%. The poor prognosis of the disease is associated with late diagnosis and a high degree of drug resistance has not been overcome during the past decades. Gemcitabine-based regimens are the first line therapy for advanced pancreatic cancer but are not curative. Recent new combination chemotherapies achieved significant benefits but toxicity makes their use controversial. Novel approaches are currently being developed; in particular cancer gene therapies are undergoing preclinical and clinical validation and are the topic of the present review. We will present different ways to design gene therapy against pancreatic cancers that have been validated in preclinical studies. We also reviewed the clinical trials already published or still ongoing.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive cancer with a high mortality rate in a time window very near the discovery of the disease
There is one clinical trial still recruiting, combining the transfer of the deoxycytidine kinase and the uridyl monophosphate kinase sensitizing the tumor cells to gemcitabine with the transfer of the gene encoding the somatostatin receptor subtype 2 (SSTR2), which behaves as a tumor suppressor (Table 2) [58]
Despite the numerous pre-clinical studies testing pancreatic cancer gene therapy, very few strategies have been transferred in clinical trials
Summary
Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive cancer with a high mortality rate in a time window very near the discovery of the disease. Because other therapeutic options failed to be efficient in controlling the progression of pancreatic cancers, the field of cancer gene therapy is currently in an active state of preclinical and clinical investigations for this disease. We published a report showing the delivery of the HSV-TK gene with a lentivirus pseudotyped to target tumor-specific cell surface antigens [30].
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