“During the last years increasing evidence implies that human cytomegalovirus (CMV) can be attributed to human malignancies arising from numerous tissues. In this perspective, we will review and discuss the potential mechanisms through which CMV infection may contribute to brain tumors by affecting tumor cell initiation, progression and metastasis formation. Recent evidence also suggests that anti-CMV treatment results in impaired tumor growth of CMV positive xenografts in animal models and potentially increased survival in CMV positive glioblastoma patients. Based on these observations and the high tumor promoting capacity of this virus, the classical and novel antiviral therapies against CMV should be revisited as they may represent a great promise for halting tumor progression and lower cancer deaths.”
Archives For medulloblastoma
The following article explains how CMV or Cytomegalovirus recreates the Hallmarks of Cancer. The following are all signs of cancer: high prevalence of cell growth signaling, evading and disabling growth suppression, resisting cell death procedures, thus enabling cell immortality, building new blood vessels and enabling invasion and thus metastasis. Chronic inflammation also plays a role in cancer progression as well. Now see Hallmark by Hallmark how CMV can recreate all of these drivers that together enable cancer.
Many factors contribute to Cancer, but the key catalyst (even the underlying engine) is one of many Viruses, particularly CMV, but also VZV, Epstein Barr as well as other Viruses SV-40, BK, JCV and HPV. Each cancer in our body has one to many viruses associated with it. Some key ones are HPV – Human Papilloma Virus causes Cervical, Anal, Mouth, Throat, Lung, Vaginal and Penile Cancers. Epstein Barr causes Lymphoma, JC Polyoma Virus causes Colon Cancer. Epstein Barr, HPV & CMV have all been associated with Breast Cancer, thus one reason for it’s prevalence. Now down to kids Cancer, Medulloblastoma Neuroblastoma and it’s 99% terminal twin cancer Glioblastoma. For these cancers its mainly CMV (Human Cytomegalovirus), though other viruses like SV-40, JC and BK are also capable and have been found in these tumors.
Genes are biological chemical software routines that do specific tasks in our bodies. Oncogenes are genes that have been proven to contribute to the development and growth of cancer. There are approx. 50 distinct Oncogenes known and some that are found often over expressed in Medulloblastoma are MYC , MYCN and TAG. MYC and MYCN alone cause many hallmarks of cancer. When these genes are ran, they accelerate DNA replication, they turn off programmed cell death in two ways, drives new blood vessels to the cell / tumor and more (footnote ***).
Anti-Oncogenes are genes with the ability to police Oncogenes and keep them from going out of control and causing cancer (The most common damaged Medulloblastoma Anti-oncogene is P53 also known as TP53. There are two copies of TP53 and both must be damaged for this gene to be silenced (footnotes * **). When cancer happens, a couple basic things happen:
New England Journal of Medicine
Cytomegalovirus (CMV) DNA and proteins are expressed in several types of human cancers and metastases1 but not in healthy surrounding tissues, suggesting a possible role for the virus in the cancer.2 The malignant brain tumor glioblastoma has a dismal prognosis, with a median overall survival of 12 to 14 months and a 2-year survival of 15 to 26%. We examined more than 250 cases of glioblastoma (Fig. S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). Of these patients, only 1 was CMV-negative. Of the 75 patients we evaluated, the median rate of overall survival was 33 months in those with low-grade CMV infection and 13 months in those with high-grade CMV infection (P=0.04); the median rates of 2-year survival were 63.6% and 17.2%, respectively (P=0.003),3 which suggests that CMV affects tumor progression.
In an animal model, anti-CMV treatment reduced the growth of medulloblastoma by 72%.4 In the Valcyte Treatment of Glioblastoma Patients in Sweden (VIGAS) study,5 a double-blind clinical trial of valganciclovir involving 42 patients with glioblastoma, we found that tumor growth (the primary end point) was not significantly reduced at 3 and 6 months after surgery. However, in exploratory analyses, 22 patients receiving at least 6 months of antiviral therapy, as compared with contemporary controls, had an increased rate of 2-year survival (50% vs. 20.6%, P<0.001) and increased median overall survival (24.1 vs. 13.7 months, P=0.003). The ethics committee approved the experimental treatment protocol for patients enrolled in the VIGAS study. Owing to the promising results of this study, 28 patients at our hospital have received anti-CMV therapy for compassionate use in addition to their standard therapy (Section S2 in the Supplementary Appendix). Patients in the VIGAS study and those who were treated for compassionate use provided written informed consent for analyses of biologic samples and outcomes. Approval by the institutional review board was not required.
Here we present current retrospective data on 50 patients with glioblastoma who received valganciclovir as an add-on to standard therapy at Karolinska University Hospital as adjuvant treatment (Section S2 in the Supplementary Appendix). The rate of survival of treated patients was remarkably high: at 2 years, 62% were alive, as compared with 18% of contemporary controls with a similar disease stage, surgical-resection grade, and baseline treatment (P<0.001) (Figure 1AFIGURE 1
Kaplan–Meier Estimates of Overall Survival in Patients with Glioblastoma Receiving Antiviral Therapy against Cytomegalovirus (CMV).
, and Table S1 in the Supplementary Appendix). The median overall survival was 25.0 months, as compared with 13.5 months in the controls (P<0.001). The median survival was higher among 40 patients who received at least 6 months of valganciclovir; their 2-year rate of survival was 70%, and their median overall survival was 30.1 months (P<0.001) (Figure 1B). The survival rate was highest among 25 patients who received continuous valganciclovir treatment after the first 6 months, with a 2-year survival rate of 90% and median overall survival of 56.4 months (P<0.001) (Figure 1C). It is unlikely that any bias in patient selection could have resulted in these high rates of survival. Our results highlight the need for a randomized trial targeting CMV in patients with glioblastomas.
The human cytomegalovirus (HCMV) and glioma sym- posium was convened on April 17, 2011 in Washington, DC, and was attended by oncologists and virologists involved in studying the relationship between HCMV and gliomas. The purpose of the meeting was to reach a consensus on the role of HCMV in the pathology of gliomas and to clarify directions for future research. First, the group summarized data that describe how HCMV biology overlaps with the key pathways of cancer. Then, on the basis of published data and ongoing research, a consensus was reached that there is sufficient evidence to conclude that HCMV sequences and viral gene expression exist in most, if not all, malig- nant gliomas, that HCMV could modulate the malig- nant phenotype in glioblastomas by interacting with key signaling pathways; and that HCMV could serve as a novel target for a variety of therapeutic strategies. In summary, existing evidence supports an oncomodula- tory role for HCMV in malignant gliomas, but future studies need to focus on determining the role of HCMV as a glioma-initiating event.
“HCMV can also do every one of the things that generally considered the 10 hallmarks ofcancer,” says Kalejta, a member of the McArdle Laboratory for Cancer Research, Carbone Cancer Center, Stem Cell and Regenerative Medicine Center and Institute for Molecular Virology at UW-Madison.
“We have confirmed the presence of active CMV infection in 99% of malignant Glioblastoma tumors and in 90% of Medulloblastoma and Neuroblastoma tumors.”
“Will Anti-Viral drugs give new hope for malignant Glioblastoma patients?”