New targeted therapies in pancreatic cancer

Abstract

Patients with pancreatic cancer have a poor prognosis with a median survival of 4-6 mo and a 5-year survival of less than 5%. Despite therapy with gemcitabine, patient survival does not exceed 6 mo, likely due to natural resistance to gemcitabine. Therefore, it is hoped that more favorable results can be obtained by using guided immunotherapy against molecular targets. This review summarizes the new leading targeted therapies in pancreatic cancers, focusing on passive and specific immunotherapies. Passive immunotherapy may have a role for treatment in combination with radiochemotherapy, which otherwise destroys the immune system along with tumor cells. It includes mainly therapies targeting against kinases, including epidermal growth factor receptor, Ras/Raf/mitogen-activated protein kinase cascade, human epidermal growth factor receptor 2, insulin growth factor-1 receptor, phosphoinositide 3-kinase/Akt/mTOR and hepatocyte growth factor receptor. Therapies against DNA repair genes, histone deacetylases, microRNA, and pancreatic tumor tissue stromal elements (stromal extracellular matric and stromal pathways) are also discussed. Specific immunotherapies, such as vaccines (whole cell recombinant, peptide, and dendritic cell vaccines), adoptive cell therapy and immunotherapy targeting tumor stem cells, have the role of activating antitumor immune responses. In the future, treatments will likely include personalized medicine, tailored for numerous molecular therapeutic targets of multiple pathogenetic pathways.

Pancreatic cancer from bench to bedside: molecular pathways and treatment options

“…Unfortunately genetically heterogenicity has been observed in pancreatic cancer (30), however; there are several targeted therapies as treatment options, such as; small molecule inhibitors and monoclonal antibodies which inhibit constitutively-active cell surface signaling molecules. Currently results of phase I-III clinical trials presented by Seicean et al (31) did not present favorable results due to the resistance from KRAS2 mutations and upregulation of alternate signaling pathways (13,32). Until now only the tyrosine kinase inhibitor of epidermal growth factor receptor, "erlotinib", has been approved agent, in combination with gemcitabine, and offers increase in survival of two weeks (33) (Figure 1).…”

Sclareolide enhances gemcitabine-induced cell death through mediating the NICD and Gli1 pathways in gemcitabine-resistant human pancreatic cancer

“…At present, the primary form of treatment for pancreatic cancer is surgery combined with chemotherapy (2). Gemcitabine is the first-line chemotherapeutic drug used clinically for the treatment of pancreatic cancer and, although gemcitabine can significantly inhibit the growth of pancreatic cancer, the emergence of gemcitabine resistance in reduces the therapeutic effect of gemcitabine, leading to shortened patient survival rates, which for the majority is only a few months (3,4).…”

Impact of Metformin on Advanced Pancreatic Cancer Survival: Too Little, Too Late?

“…Both regimens have been shown to offer only modest mortality benefit. More recently, immunotherapy offers potential promise (5). …”