mTOR expression in pancreatic adenocarcinoma and its correlation with survival

Rajan, Anand; Tolocica, Ioana; El‐Zammar, Ola; Chittoria, Namita; Singh, Mansher; Newman, Nancy; Gajra, Ajeet

doi:10.1200/jco.2008.26.15_suppl.22169

Cited by 2 publications

(3 citation statements)

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“…Other agents, including everolimus and sirolimus, are currently in phase II clinical trials 56. A combination of an mTOR inhibitor with other standard or targeted therapies might be needed,57,58 as mTOR expression does not correlate with survival of patients 59…”

Section: Other Potential Therapeutic Targetsmentioning

confidence: 99%

Pancreatic cancer: molecular pathogenesis and new therapeutic targets

Wong

Lemoine

2009

Nat Rev Gastroenterol Hepatol

187

158

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Patients with pancreatic cancer normally present with advanced disease that is lethal and notoriously difficult to treat. Survival has not improved dramatically despite routine use of chemotherapy and radiotherapy; this situation signifies an urgent need for novel therapeutic approaches. Over the past decade, a large number of studies have been published that aimed to target the molecular abnormalities implicated in pancreatic tumor growth, invasion, metastasis, angiogenesis and resistance to apoptosis. This research is of particular importance, as data suggest that a large number of genetic alterations affect only a few major signaling pathways and processes involved in pancreatic tumorigenesis. Although laboratory results of targeted therapies have been impressive, until now only erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has demonstrated modest survival benefit in combination with gemcitabine in a phase III clinical trial. Whilst the failures of targeted therapies in the clinical setting are discouraging, lessons have been learnt and new therapeutic targets that hold promise for the future management of the disease are continuously emerging. This Review describes some of the important developments and targeted agents for pancreatic cancer that have been tested in clinical trials.

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Section: Other Potential Therapeutic Targetsmentioning

confidence: 99%

Pancreatic cancer: molecular pathogenesis and new therapeutic targets

Wong

Lemoine

2009

Nat Rev Gastroenterol Hepatol

187

158

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“…In breast cancer, p-mTOR expression is predominantly detected in the cytoplasm and is significantly associated with short RFS, but does not correlate with any clinicopathological factors, including stage, histological grade, and lymph node involvement (Zhou et al, 2004). Rajan et al found that p-mTOR expression is unrelated to survival in pancreatic cancer (Rajan et al, 2008). Boone et al reported that p-mTOR expression is only associated with a lesser degree of tumour differentiation (Boone et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…The anticancer effect of RAD001, a rapamycin analogue, has also been shown in advanced gastric cancer (Muro et al, 2008). However, few studies have assessed correlations of mTOR expression in human cancers with either clinocopathological features or outcomes (Zhou et al, 2004;Rajan et al, 2008).…”

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confidence: 99%

Relation between outcomes and localisation of p-mTOR expression in gastric cancer

et al. 2009

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The mammalian target of rapamycin (mTOR), a Ser/Thr protein kinase that mediates intracellular signalling related to cell growth, proliferation, and differentiation, has received considerable interest as a possible target for cancer treatment. We evaluated the correlation of mTOR expression with clinicopathological features, outcomes, and the expression of Akt, an upstream regulator of mTOR, in gastric cancer. Tumour samples were obtained from 109 patients with gastric adenocarcinomas who underwent a radical gastrectomy. The expressions of phosphorylated mTOR (p-mTOR) and phosphorylated Akt (p-Akt) in the cytoplasm and in the nucleus were analysed by immunohistochemical staining. Cytoplasmic p-mTOR expression positively correlated with the depth of tumour invasion (T1 vs T2 -4, P ¼ 0.003), involved lymph nodes (P ¼ 0.010), and tumour stage (I vs II -IV, P ¼ 0.002). In contrast, nuclear p-mTOR expression negatively correlated with these variables (Po0.001, ¼ 0.035, and o0.001). Cytoplasmic p-mTOR expression was associated with significantly poorer relapse-free survival (RFS, P ¼ 0.037) and overall survival (OS, P ¼ 0.024), whereas nuclear p-mTOR expression was associated with better RFS and OS (P ¼ 0.029, 0.059). Neither cytoplasmic nor nuclear p-Akt expression was associated with any clinicopathological factor or with survival. Localisation of p-mTOR may play an important role in tumour progression and outcomes in patients with gastric cancer.

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mTOR expression in pancreatic adenocarcinoma and its correlation with survival

Cited by 2 publications

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Pancreatic cancer: molecular pathogenesis and new therapeutic targets

Pancreatic cancer: molecular pathogenesis and new therapeutic targets

Relation between outcomes and localisation of p-mTOR expression in gastric cancer

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