The presence of active cytomegalovirus proteins and nucleic acids has been found in both Glioblastoma and Medulloblastoma tumours, and more recently and in other cancers such as ovarian cancer, breast cancer, prostate cancer and colorectal cancer, especially in secondaries.
What is Cytomegalovirus?
Cytomegalovirus (CMV), also referred to as Human Cytomegalovirus (HCMV) is a double-stranded DNA virus. CMV is a beta-herpes virus, the cousin of the cold sores' virus and of HPV. It is found in 80 per cent of humans but lies dormant in cells, rather like Herpes 4 or EBV. Herpes 1 and 8, and HPV can also lie dormant, but in the nerves.
CMV and brain cancer
CMV, which is found in 80 per cent of humans but normally lies dormant, was found in 2002 by neuro-surgeon Charles Cobb of UCSF to be 'active' in the tumours of the 24 brain samples he reviewed. Moreover, in the adjacent healthy tissue Cobbs found the virus to be dormant. He published his study but most researchers could not find a similar result. However, a team from Duke University led by neuro-surgeon Duane Mitchell finally did publish a peer-reviewed confirmation of Cobb's work. "We have enough evidence now to say that this merits serious attention," said Mitchell (1).
In 2012, Swedish researchers found a high prevalence of active cytomegalovirus proteins and nucleic acids in different brain cancer tumours. However, they found healthy, non-cancer cells in close proximity to the tumours consistently virus negative (2). Importantly, the researchers stated that 'CMV confers both oncogenic and onco-modulatory mechanisms'.
By 2015 the researchers were increasingly clear. In further research (3), they stated that CMV did lie behind brain cancer - tumour cell initiation, progression and metastasis formation - and that treating CMV in animals with brain cancer impaired tumour growth.
And according to a 2019 study (4), CMV affects tumour stem cell factors, angiogenesis and immune pathways in brain cancer.
CMV has also been found active in 93 per cent of Medulloblastoma tumours (5). And a 2015 study by researchers at the California Pacific Medical Center explored the connection between CMV and glioma stem-like cells ("GSC"). Long-term, low-level CMV infection may promote the survival, 'stemness', and proliferation of glioma stem-like cells and could significantly contribute to GBM pathogenesis. (Glioma stem-like cells, as in other cancers, have the ability for self-renewal and cancer recurrence, and are resistant to chemo and radiotherapy). CMV infected Glioma cells out live their uninfected peers.
What might attack CMV and increase survival times?
Anti-viral studies targeting CMV antigens using expanded T-cells or dendritic cell vaccines seem to offer promise and larger studies are underway.
Natural compounds may help. A 2013 study showed that an extract of Elaeocarpus sylvestris inhibited CMV immediate early gene expression and replication (6). And a 2015 study (7) showed high dose turmeric (or curcumin) could inhibit CMV by down-regulating heat shock protein 90. A study on mushroom varieties with CMV showed that Oyster mushrooms and Shiitake could have a significant effect (20).
But, for oncologists, of most interest to date has been the drug Valcyte or Valganciclovir:
* In a retrospective study at Vanderbilt University of 13 GBM patients who received Valcyte with Avastin (Bevacizumab), the 6 month survival and progression free survival had climbed from 34 per cent to 62 per cent, and 8.7 months to 13.1.The researchers actually commented that Avastin does not particularly increase brain cancer survival, and offered that the increased survival was principally due to the anti-CMV drug (8). Clearly a better study with more people is required.
* In a review (9) by the above Swedish team from the Karolinska Institute, 102 GBM patients between December 2006 and November 2019, received Valcyte as an 'add-on' treatment. The control group number 231 patients not receiving Valcyte. The Valcyte group reported no increased toxicity. The patients taking Valcyte had a longer median survival - up from 13.3 months to 24.1 months - and a much greater 2-year survival rate - an increase from 17.3 per cent to 49.8 per cent. There was no difference between patients whose cancers were methylating or non-methylating. The researchers concluded Valcyte was safe to use. and, on its own, was capable of dramatic and significant increases in overall survival times.
What is Valcyte, or Valganciclovir?
Valganciclovir, sold under the name Valcyte and others, is an antiviral medicine used to treat CMV. It is often given for long term use as, some experts argue, it may only suppress the virus rather than providing a cure (10). It may also be used as a preventative agent, for example during kidney transplants (11) as infection by CMV during the transplant seems to cause a greater likelihood of rejection. Side effects can be serious and include fever, chills, tiredness, flu symptoms, mouth sores, skin sores, pale skin, easy bruising, unusual bleeding, shortness of breath, or feeling light-headed. It can cause birth defects if either of the parents were using it at the time of conception. Some experts suggest the drug may even cause certain cancers. The drug is taken by mouth.
Significantly, the drug is now off patent and is cheap to use.
What about CMV and other cancers?
There is a strong link between inflammation, Cox-2 and PGE2 and tumour development, both Cox-2 and PEG2 being over expressed in a number of cancer tumours. and high Cox-2 presence is linked to a poor prognosis. CMV infection is linked to the levels of both Cox-2 and PEG2, and this breeds inflammation, causes the generation of a tumour, induces cellular proliferation, angiogenesis, and stimulates cellular invasion.
Of course, anyway, viruses just through their presence can cause an immune response.
By 2015, the idea that CMV might lie behind several cancers was growing in acceptance. But then Epstein-Barr (sometimes referred to as Herpes 4) had been connected to lymphoma, Hepatitis B to liver cancer and HPV to cervical cancer. And CMV had been found present in higher levels in some patients with breast cancer, colon cancer, and prostate cancer, hepatocellular cancer, salivary gland tumors, some sarcomas, neuroblastoma not only brain tumors.
CMV and breast cancer
To put this into perspective, more than 90 per cent of breast cancer tumours have been found to be CMV positive. And CMV has been found active in primary breast cancer tumours and in Sentinel node tissue (12).
In a 2019 Review of Human cytomegalovirus (HCMV) and breast cancer (13), it was confirmed that classical human onco-viruses are estimated to play a role during carcinogenesis in 15–20% of cancer cases. Although the DNA and gene products of several onco-viruses have been found in breast tumors, there was no definitive proven link to the initiation of breast cancer until recently. 'CMV gene products are found in >90% of breast cancer tumors and metastases of breast cancers, and they have been linked to more aggressive breast cancer'.
A specific HCMV strain, HCMV-DB, has now been shown to cause cancer activity in normal breast cells in vitro, and even to give rise to fast-growing, triple-negative breast tumours when injected into immune deficient mice.
In clinical studies increased HCMV protein expression is found in triple negative breast cancer biopsies. HCMV is known to promote breast cancer and suppress the immune system changing the cellular environment. HCMV-infected cells can even avoid detection and elimination by the immune system by inhibiting macrophages and T-cells.
A 2020 meta-analysis (21) concluded that CMV could be causal for different types of breast cancer and vaccines to prevent the CMV action were on their way..
CMV and prostate cancer
In prostate cancer, a 2006 study (14) suggested that CMV could promote spread of prostate cancer, and a 2012 study (15) showed high infection rates but no evidence of cause.
CMV and colorectal cancer
In colorectal cancer, a 2016 meta-analysis (16) starts by saying that Human Cytomegalovirus (HCMV) is considered a factor in tumorigenesis; and after reviewing all available research at that time concludes that 'there is a statistical association between HCMV infection and the risk of Colorectal cancer'.
CMV and Ovarian Cancer, and Chemotherapy
In November 2023, research (19) from a team at the University of Minnesota, showed that CMV was active in 29.2% of Ovarian cancer patients. If one in three doesn't sound too bad to you, let me add this: When those women had 3 rounds of chemotherapy, the numbers testing positive for active CMV rose to 60.2%.
After finishing chemotherapy, the numbers testing positive for CMV fell back to 31.3%. Part of the study looked at Cancer-Related Cognitive Impairment following Chemotherapy.. This was found to be significantly higher in those who had CMV on diagnosis.
CMV and the pancreas and liver
And here's another issue. Cytomegalovirus in people with a strong immune system is dormant and the person is typically asymptomatic. Sometimes it might give mild, flu-like symptoms. However in immunocompromised people CMV can cause significant disease. Pancreatitis is one such disease and the patient recovered with the use of Ganciclovir. There is no research-based link to Pancreatic cancer, but CMV cannot be ruled out. The same study (22) and others refer to CMV interaction with EBV. For example, CMV and EBV have been linked to Hepatitis (23).
CMV and cancer - a summary
CANCERactive founder and former Oxford University Biochemist summariased the issues with CMV thus : "CMV is present and dormant in at least 80 per cent of healthy adults. However it certainly seems to be active in most, if not all, primary brain tumours. It doesn't stop there! CMV has been found to be active in some primary breast, ovarian and colorectal cancers and certainly appears to be involved in aggressive metastatic cancers. It is also found active in secondary brain tumours. Research suggests CMV can be involved in tumour initiation, angiogenesis, growth, proliferation and metastasis. It also seems to be a contributor to cognitive decline following chemotherapy.
For the moment Valcyte is the only drug with any research to support its role in increasing cancer survival (but only with brain cancer). Natural compounds such as Turmeric, Elaeocarpus sylvestris (17), and two mushroom varieties Pleurotus (Oyster mushrooms) and Lentinus (Shiitake) (20) seem to be beneficial.
Other antiviral compounds are known to be effective with the Herpes family; for example, Pau d'arco and Olive Leaf Extract are known to restrict Herpes variants and AHCC, another natural compound from Shiitake mushrooms can attack HPV; Cordycepin can attack Epstein Barr.
We also have recent research that suggests that Covid spike protein can turn on dormant Varicella (shingles) which can turn on dormant viruses such as Herpes 1 and 8 in a chain reaction and trigger illness including dementia (18).
There are some reports that the action of Valganciclovir may be enhanced by the use of off-label drug Low Dose Naltrexone, known to enhance the immune system."
Go to: Review: Parasites, Viruses, Yeasts and cancer
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References
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Newsweek - https://www.newsweek.com/cancer-there-brain-tumor-virus-77933
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Cytomegalovirus in brain tumors Oncoimmunology. 2012 Aug 1; 1(5): 739–740. doi: 10.4161/onci.19441
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Cytomegalovirus in human brain tumors: Role in pathogenesis and potential treatment options; Cecilia Söderberg-Nauclér, John Inge Johnsen; World J Exp Med. 2015 Feb 20; 5(1): 1–10 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4308527/
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Oncoimmunology. 2019; 8(1): e1514921. Published online 2018 Oct 16. doi: 10.1080/2162402X.2018.1514921
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Detection of human cytomegalovirus in medulloblastomas; Baryawno N et al. J Clin Invest. 2011;121:4043–4055
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Elaeocarpus sylvestris and CMV - https://www.spandidos-publications.com/10.3892/mmr.2013.1824
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Curcumin and CMV - https://www.spandidos-publications.com/10.3892/mmr.2015.3983
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Valganciclovir and bevacizumab for recurrent glioblastoma, Mol Clin Oncol. 2016 Feb; 4(2): 154–158.
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Valganciclovir as Add-on to Standard Therapy in Glioblastoma Patients; Clin Cancer Res
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Wikipedia - https://en.wikipedia.org/wiki/Valganciclovir
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Drugs.com - https://www.drugs.com/mtm/valcyte.html
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High prevalence of human cytomegalovirus proteins and nucleic acids in primary breast cancer
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Review of HCMV and breast cancer: Cancers (Basel). 2019 Dec; 11(12): 1842. Published online 2019 Nov 22. doi: 10.3390/cancers11121842
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Human Cytomegalovirus Infection Alters PC3 Prostate Carcinoma Cell Adhesion
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Prostate cancer and HCMV - Cancer Causes Control. 2012 Sep; 23(9): 1511–1518. Published online 2012 Jul 19. doi: 10.1007/s10552-012-0028-5
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Human cytomegalovirus and colorectal cancer - a meta-analysis.
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The extract of Elaeocarpus sylvestris inhibits human cytomegalovirus; Kim Phuong To; Nov 2013
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Viruses can interact to trigger Alzheimer's
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Prevalence of active cytomegalovirus infection at diagnosis of ovarian cancer and during chemotherapy
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In Vitro Search for Antiviral Activity against Human CMV; Roy D et al; J Antivir Antiretrovir.12, 2020
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Breast cancer and cytomegalovirus; AK Richardson et al; ;Clin and Trans Oncology vol 22, 585–602 (2020)
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Cytomegalovirus pancreatitis in an immunocompetent patient; Muhammad I. Saeed et al; IDCases. 2020; 22
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Epstein-Barr Virus and Cytomegalovirus Infections of the Liver; Gastroenterol Clin North Am; 2020 Jun;49(2):331-346.
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