Multimodality Approaches for Pancreatic Cancer

Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
CA A Cancer Journal for Clinicians (Impact Factor: 115.84). 11/2005; 55(6):352-67. DOI: 10.3322/canjclin.55.6.352
Source: PubMed


The role of combined-modality therapy for pancreatic cancer is evolving with the recent development and completion of major, multi-institutional clinical trials. One of the challenges for the busy clinician is to appreciate the variation in staging, surgical expertise, and application of either definitive chemoradiotherapy or adjuvant chemoradiotherapy for local and/or regionally advanced disease. Our aim is to summarize the current state-of-the-art management and future directions regarding the multimodality approach to pancreatic cancer.

5 Reads
  • Source
    • "Indeed, PDAC cell invasion occurs very early in the disease maybe even before the formation of an identifiable primary tumor [2]. Therefore, although surgery remains the cornerstone of cure, the need for adjuvant treatment modalities is of critical importance [3]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers principally because of early invasion and metastasis. The epidermal growth factor receptor (EGFR) is essential for PDAC development even in the presence of Kras, but its inhibition with erlotinib gives only a modest clinical response, making the discovery of novel EGFR targets of critical interest. Here, we revealed by mining a human pancreatic gene expression database that the metastasis promoter Na(+)/H(+) exchanger (NHE1) associates with the EGFR in PDAC. In human PDAC cell lines, we confirmed that NHE1 drives both basal and EGF-stimulated three-dimensional growth and early invasion via invadopodial extracellular matrix digestion. EGF promoted the complexing of EGFR with NHE1 via the scaffolding protein Na+/H+ exchanger regulatory factor 1, engaging EGFR in a negative transregulatory loop that controls the extent and duration of EGFR oncogenic signaling and stimulates NHE1. The specificity of NHE1 for growth or invasion depends on the segregation of the transient EGFR/Na+/H+ exchanger regulatory factor 1/NHE1 signaling complex into dimeric subcomplexes in different lipid raftlike membrane domains. This signaling complex was also found in tumors developed in orthotopic mice. Importantly, the specific NHE1 inhibitor cariporide reduced both three-dimensional growth and invasion independently of PDAC subtype and synergistically sensitized these behaviors to low doses of erlotinib. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.
    Neoplasia 02/2015; 17(2):155. DOI:10.1016/j.neo.2014.12.003 · 4.25 Impact Factor
  • Source
    • "Indeed, PDAC cell invasion occurs very early in the disease maybe even before the formation of an identifiable primary tumor [2]. Therefore, although surgery remains the cornerstone of cure, the need for adjuvant treatment modalities is of critical importance [3]. "

    Frontiers in Pharmacology 01/2014; 5. DOI:10.3389/conf.fphar.2014.61.00012 · 3.80 Impact Factor
  • Source
    • "It is interesting that these types of cancers show frequent alternation in Kisten-Ras (K-Ras: Jones et al., 2008; Ding et al., 2008). In particular, oncogenic mutation of K-Ras is a predominant event in pancreatic cancer (Jones et al., 2008), the survival rate of which is less than 5% (Yang et al., 2005; Jones et al., 2008). As oncogenic Ras induces cell death and senescence through p53 activation, it is generally accepted that oncogenic Ras-mediated tumor formation should be achieved under a p53-deficient condition. "
    [Show abstract] [Hide abstract]
    ABSTRACT: p53 is eliminated from K-Ras-mutated cancer cells through direct interaction with Snail. However, it is not achieved through proteasome-mediated degradation or transcriptional repression. Here we provide evidence that p53, binding with Snail, is exported from a K-Ras-mutated cell through a vesicle transport-like mechanism, independently using a p53-nuclear-exporting mechanism. Although we can detect p53 in culture media, a majority of p53 might be degraded by extracellular proteases. Thus, we can recover the secreted p53 in culture media by the inhibition of protease and endocytosis. In addition, a considerable amount of p53 is endocytosed by neighboring cells. As p53 resorption occurs in a K-Ras-dependent manner, treatment of recombinant p53 is detected in the whole-cell lysate of K-Ras-mutated cells, but not in that of wild-type cells. Using the property of p53, we can deliver the chemical (propidium iodine) into K-Ras mutated cells selectively. In contrast, Snail, a co-secreted protein with p53 in response to oncogenic K-Ras, shows resistance to endocytosis and protease, and results in remaining in the media. Thus, we can detect an autoantibody against Snail in the serum of a human cancer patient. Our finding can be used for a mutant K-Ras-specific anticancer drug delivery system and for the diagnosis of pancreatic, colon and lung cancers.
    Oncogene 05/2009; 28(19):2005-14. DOI:10.1038/onc.2009.67 · 8.46 Impact Factor
Show more

Similar Publications