Frequent detection of human cytomegalovirus in neuroblastoma: A novel therapeutic target?

Neuroblastoma is the most common and deadly tumor of childhood, where new therapy options for patients with high‐risk disease are highly warranted. Human cytomegalovirus (HCMV) is prevalent in the human population and has recently been implicated in different cancer forms where it may provide mechanisms for oncogenic transformation, oncomodulation and tumor cell immune evasion. Here we show that the majority of primary neuroblastomas and neuroblastoma cell lines are infected with HCMV. Our analysis show that HCMV immediate‐early protein was expressed in 100% of 36 primary neuroblastoma samples, and HCMV late protein was expressed in 92%. However, no infectious virus was detected in primary neuroblastoma tissue extracts. Remarkably, all six human neuroblastoma cell lines investigated contained CMV DNA and expressed HCMV proteins. HCMV proteins were expressed in neuroblastoma cells expressing the proposed stem cell markers CD133 and CD44. When engrafted into NMRI nu/nu mice, human neuroblastoma cells expressed HCMV DNA, RNA and proteins but did not produce infectious virus. The HCMV‐specific antiviral drug valganciclovir significantly reduced viral protein expression and cell growth both in vitro and in vivo. These findings indicate that HCMV is important for the pathogenesis of neuroblastoma and that anti‐viral therapy may be a novel adjuvant treatment option for children with neuroblastoma.     

Is there a role for Notch signalling in human breast cancer?

Aberrant Notch signalling has been observed in several human cancers, including acute T-cell lymphoblastic leukaemia and cervical cancer, and is strongly implicated in tumourigenesis. Unregulated Notch signalling in the mouse mammary gland leads to tumour formation. These results raise the possibility that Notch signalling might play a role in human breast cancer. There are currently few reports that address this question directly and this appears to be an area worthy of further investigation.     

Sphingosin-1-phosphate as a target for cancer therapy

Phospholipids and their derivatives were considered"neutral"in that they were thought either to serve a simple structural role in cell membrane organization or to provide energy for beta oxidation,glycolysis and other metabolic processes.It has only recently been appreciated that many lipids play significant roles as bioactive signaling mediators. Sabbadini in a minireview in Brit J Cancer(2006,95:1131-1135)summarized the role of sphingolipid,a group of signaling molecules with pteiotropic effects,in carcinogenesis.The key dements of the sphingolipid signaling cascade include such bioactive lipid mediators as ceramide(CER),ceramide-1-phosphate(CIP),sphingosine(SPH)and     

VAV1: a new target in pancreatic cancer?

Pancreatic ductal adenocarcinoma (PDA) is arguably the most lethal malignancy in the United States. Despite the identification of many molecular alterations in PDA, this information has not translated into effective therapeutic strategies to date. A recent report in Cancer Cell (Fernandez-Zapico et al, Cancer Cell 2005, 7:39-49) reveals an unexpected role for the hematopoietic-specific RhoGEF VAV1 in pancreatic tumorigenesis, where ectopic expression of VAV1 as a result of promoter demethylation was identified in the majority of established cell lines and PDA tissue samples. Importantly, VAV1 expression was functionally required for optimal proliferation, transformation and survival of pancreatic cancer cell lines. This study provides the first evidence of VAV1 promoter demethylation as an event in cancer progression, suggesting that aberrant signaling pathways driven by VAV1 are potential therapeutic targets in PDA.     

Multimodality therapy in inflammatory breast cancer: Is there a place for surgery?

Background:In many centres surgery is used as part of a combinedmodality approach to the treatment of inflammatory breast cancer (IBC).Nevertheless, its value is controversial given the high risk of metastaticrelapse and poor overall prognosis. We have reviewed patients with true IBCprospectively treated at the Royal Marsden Hospital in chemotherapy trials toassess further the role of surgery as part of combined modality treatment. Patients and methods:Fifty-four patients who had responsive orstable disease to primary chemotherapy went on to have either radiotherapyalone (n = 35) or surgery plus radiotherapy (n = 19); thedecision on surgery was based partly on clinician preference and partly onclinical response. Results:The 35 patients undergoing radiotherapy alone had amedian progression-free survival (PFS) of 16 months and median overallsurvival (OS) of 35 months. Twenty-four patients (69%) have relapsedwith a total of twelve (34%) relapsing locally. In comparison, the 19patients receiving both surgery and radiotherapy had a PFS of 20 months, anda median OS of 35 months. Fifteen patients (79%) have relapsed, eight(42%) of these locally. None of these differences were statisticallysignificant. Conclusions:These results do not suggest a clinical advantage forsurgery in addition to chemotherapy and radiotherapy for patients with IBC.They support the need for a prospective randomised trial to address thisquestion.