Novel approaches to target pancreatic cancer.
ABSTRACT Despite remarkable progress that has been made in the recent years in the treatment of gastrointestinal tumors, in particular colorectal cancer, the prognosis of pancreatic cancer remains dismal. Five years after diagnosis almost all patients have died. At early stages of the disease surgery is the only modality to achieve long term survival. In the palliative setting gemcitabine confers some benefit to patients with advanced pancreatic cancer. A large number of chemotherapy combinations has been tested in patients with advanced pancreatic cancer. Only one combination showed significant improvement of survival, however also increased toxicity. The introduction of targeted therapies raised hopes for a better treatment of pancreatic cancer. However, most of the compounds tested so far failed to improve the survival of patients with pancreatic cancer. This review summarizes molecular targets examined so far in pancreatic cancer including matrix metalloproteinase inhibitors, farnesyltransferase inhibitors, vascular endothelial growth factor and epidermal growth factor receptor inhibitors and points out novel promising strategies for this difficult-to-treat tumor.
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ABSTRACT: Myc-induced nuclear antigen (Mina53) is a protein with a molecular weight of 53 kDa expression of which is induced by c-Myc. Increased expression of Mina53 is documented in some human carcinomas. In this study, we found markedly increased Mina53 expression in pancreatic cancer tissue specimens. This expression did not correlate with clinicopathological characteristics, such as sex, age, and presence of distant metastasis. However, there was a statistically significant association with histological differentiation, TNM stage, and lymph node metastases. To study functional role of Mina53, we silenced its expression by siRNA in PANC-1 cells. These cells were arrested in the G2/M phase, and apoptosis rates were increased. In conclusion, increased expression of Mina53 may play an important role in the development of human pancreatic cancer. Mina53 can be used as a marker for pancreatic cancer and may potentially be exploited as a target for treatment of pancreatic cancer.Cell biochemistry and biophysics 02/2014; · 3.34 Impact Factor
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ABSTRACT: In the past 15 years, we have seen few therapeutic advances for patients with pancreatic cancer, which is the fourth leading cause of cancer-related death in the United States. Currently, only about 6% of patients with advanced disease respond to standard gemcitabine therapy, and median survival is only about 6 mo. Moreover, phase III trials have shown that adding various cytotoxic and targeted chemotherapeutic agents to gemcitabine has failed to improve overall survival, except in cases in which gemcitabine combined with erlotinib show minimal survival benefit. Several meta-analyses have shown that the combination of gemcitabine with either a platinum analog or capecitabine may lead to clinically relevant survival prolongation, especially for patients with good performance status. Meanwhile, many studies have focused on the pharmacokinetic modulation of gemcitabine by fixed-dose administration, and metabolic or transport enzymes related to the response and toxicity of gemcitabine. Strikingly, a phase III trial in 2010 showed that, in comparison to gemcitabine alone, the FOLFIRINOX regimen in patients with advanced disease and good performance status, produced better median overall survival, median progression-free survival, and objective response rates. This regimen also resulted in greater, albeit manageable toxicity.World Journal of Gastroenterology 02/2012; 18(8):736-45. · 2.55 Impact Factor
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ABSTRACT: The adenovirus type 5 E1A protein (E1A) plays a critical role in anti-cancer gene therapy and has been tested in clinical trials. The expression of E1A significantly reduces tumorigenesis, promotes cell death, and inhibits cancer cell mobility. Chemosensitization is one of the anti-tumor effects of E1A, increasing in vitro and in vivo sensitization of anti-cancer drugs, including cisplatin, gemcitabine, etoposide, doxorubicin, paclitaxel, and tumor necrosis factor-related apoptosis-inducing ligand and histone deacetylase inhibitors in different types of cancer cells. E1A also demonstrates anti-metastasis activity through various molecular mechanisms such as the repression of protease expression, suppression of HER2/neu and downregulation of microRNA (miR-520h). Moreover, E1A has been reported to reprogram transcription in tumor cells and stabilize tumor suppressors such as PP2A/C, p21 and p53. Because E1A plays a potentially significant role in anti-tumor therapy, there exists an urgent need to study the anti-cancer activities of E1A. This paper presents a review of our current understanding of the tumor-suppressive functions and molecular regulation of E1A, as well as the potential clinical applications of E1A.Archivum Immunologiae et Therapiae Experimentalis 02/2014; · 2.38 Impact Factor