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Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. Michelakis ED, Webster L, Mackey JR. Br J Cancer. 2008 Oct 7;99(7):989-94. Epub 2008 Sep 2. Review. PMID: 18766181 doi:10.1038/sj.bjc.6604554 The unique metabolism of most solid tumours (aerobic glycolysis, i.e., Warburg effect) is not only the basis of diagnosing cancer with metabolic imaging but might also be associated with the resistance to apoptosis that characterises cancer. The glycolytic phenotype in cancer appears to be the common denominator of diverse molecular abnormalities in cancer and may be associated with a (potentially reversible) suppression of mitochondrial function. The generic drug dichloroacetate is an orally available small molecule that, by inhibiting the pyruvate dehydrogenase kinase, increases the flux of pyruvate into the mitochondria, promoting glucose oxidation over glycolysis. This reverses the suppressed mitochondrial apoptosis in cancer and results in suppression of tumour growth in vitro and in vivo. Here, we review the scientific and clinical rationale supporting the rapid translation of this promising metabolic modulator in early-phase cancer clinical trials More than 40 nonrandomised trials of DCA in small cohorts of patients have been reported, but the first two randomised control trials of chronic oral therapy with DCA in congenital mitochondrial diseases were reported in 2006. In the first, a blinded placebo-controlled study was performed with oral DCA administered at 25 mg kg-1 day-1 in 30 patients with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) (Kaufmann et al, 2006). Most patients enrolled in the DCA arm developed symptomatic peripheral neuropathy, compared with 4 out of 15 in the placebo arm, leading to the termination of the study. Seventeen out of 19 patients had at least partial resolution of peripheral neurological symptoms by 9 months after discontinuation of DCA. This neurotoxicity res

Safety Study of Seneca Valley Virus in Patients With Solid Tumors With Neuroendocrine Features This study is currently recruiting participants. Verified by Neotropix, September 2008 This is the first study in man of Seneca Valley Virus, a virus which seeks and kills certain tumors in non-human model systems. Subjects in this trial will be patients with advanced cancer displaying certain specified neuroendocrine features, pathologically; they will have exhausted standard methods of treatment for their tumor. The primary purpose of the trial is to determine if the virus may be administered safely. Additional purposes are to learn about the distribution of the virus in the body, the elimination of the virus from the body, the immune response to the virus and whether the virus might have some beneficial effects upon the tumors which the patients have. The first patients will be treated with low amounts of virus and subsequent patients may receive higher amounts. At the end of the trial, it is intended to select a dose for further study.

Vitamin D and intervention trials in prostate cancer: from theory to therapy. Schwartz GG. Ann Epidemiol. 2009 Feb;19(2):96-102. Epub 2008 Jul 10. PMID: 18619854 doi:10.1016/j.annepidem.2008.03.007 This suggests that whereas vitamin D (e.g., cholecalciferol) might prevent prostate cancer, existing prostate tumors likely would require treatment with 1,25(OH)(2)D and/or its analogs. The major obstacle to the use of 1,25(OH)(2)D in patients therapeutically is the risk of hypercalcemia. Several maneuvers to reduce this risk, including pulse dosing and the use of less calcemic 1,25(OH)(2)D analogs, have been explored in Phase I-III clinical trials. Once merely a promise, vitamin D-based therapies for prostate cancer may soon be medical practice.

You may have seen articles in the news about a drug called DCA (dichloroacetate), that is claimed to be cheap, safe and "kill most cancers". Understandably this has caused a great deal of interest, especially as DCA is an off-patent drug and appears to be non-toxic to humans. DCA has now been approved for a trial in brain cancer patients in Canada. The researchers have raised $800,000 in public donations to fund the trial

B. G. Redman, P. Esper, Q. Pan, R. L. Dunn, H. K. Hussain, T. Chenevert, G. J. Brewer, and S. D. Merajver Phase II Trial of Tetrathiomolybdate in Patients with Advanced Kidney Cancer Clin. Cancer Res., May 1, 2003; 9(5): 1666 - 1672.

Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007 Jun;85(6):1586-91. PMID: 17556697 [PubMed - indexed for MEDLINE]

Benefits of Vitamin D Supplementation Joel M. Kauffman, Ph.D. Journal of American Physicians and Surgeons Volume 14 Number 2 - Summer 2009 Clinical trials show that vitamin D supplementation at higher levels than previously recommended is beneficial for many conditions. It decreases the frequency of falls and fractures, helps prevent cardiovascular disease, and reduces symptoms of colds or influenza. Benefits are also seen in diabetes mellitus, multiple sclerosis, Crohn disease, pain, depression, and possibly autism. Sunlight does not cause an overdose of vitamin D production, and toxicity from supplementation is rare. Dose recommendations are increasing, but appear to be lagging the favorable trial results. A number of common drugs deplete vitamin D levels, and others may limit its biosynthesis from sunlight. People with adequate levels from sun exposure will not benefit from supplementation. While dietary intake is helpful, supplementation is better able to raise serum 25-hydroxyvitamin D , the major circulating metabolite, to the level now thought adequate, 30-50 ng/mL. Where there is inadequate daily sun exposure, oral doses of 1,000-2,000 IU/d are now considered routine, with much higher doses (up to 50,000 IU) for rapid repletion now considered safe.

beta-glucan A polysaccharide isolated from the cell walls of bacteria, plants, and fungi with immunostimulant and antineoplastic activities. In a solubilized form, beta-glucan binds to a lectin site within complement receptor 3 (CR3) on leukocytes, priming the receptor to trigger cytotoxic degranulation of leukocytes when leukocyte CR3 binds to complement 3 (iC3b)-coated tumors. Thus, the attachment of beta-glucan to CR3 of circulating leukocytes simulates leukocytes to kill iC3b-coated tumor cells in the same way as they kill iC3b-coated yeast. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

What is VITAL? The VITamin D and OmegA-3 TriaL (VITAL) is a research study in 20,000 U.S. men and women investigating whether taking daily dietary supplements of vitamin D (about 2000 IU) or fish oil (about 1 gram of omega-3 fatty acids) reduces the risk of developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses. Recruitment for the study will begin in January 2010.

Targeted cancer therapy and gene therapy have been mentioned in the blue before, but oncolytic viruses are the hot young thing. For consideration in cancer treatment, an virus must replicate in and kill a high number of exclusively cancer cells, while sparing healthy tissue. A Philadelphia-based company called Neotropix has won awards for its research into a prime contender - the Seneca Valley Virus. It has been the subject of Phase I adult clinical trials, with Phase II adult and Phase I pediatric clinical trials to start this year. SVV has advantages over some other contenders in that it is a naturally occurring (lest we create a race of mutant zombies) organism and studies so far suggest it is not harmful to healthy human cells. While a number of other oncolytic viruses are being examined, NTX-010 seems able to treat a very wide range of common and rare forms of cancer, some of which are now considered uniformly fatal. In addition, unlike some other tested viruses, it can travel through the bloodstream to treat metastatic and not just local disease. Compared to the side-effects and late effects of chemotherapy and radiation treatment, and because many of the cancers ideal for treatment with an oncolytic virus have no surgical options, this may be the next big breakthrough.

The April issue of the journal Cancer Prevention Research published the results of a trial conducted by scientists at Tokyo University of Science, the University of Tsukuba in Japan, and Johns Hopkins University which determined that the isothiocyanate sulforaphane, a compound that occurs in high amounts in broccoli and its sprouts, helps suppress infection by Helicobacter pylori (H. pylori), the bacteria responsible for stomach ulcers and many cases of stomach cancer. The trial is the first to demonstrate an effect for broccoli against H. pylori in humans.

A heat-stable extract of white button mushrooms (Agaricus bisporus) with potential chemopreventive and immunomodulating activities. Phytochemicals, such as polysaccharides and especially beta-D-glucans found in the white button mushroom extract, bind to and inhibit the activity of aromatase, an enzyme responsible for the conversion of androgens to estrogens and which is often upregulated in breast cancer cells. The consequent decrease in estrogen production may result in the suppression of estrogen-dependent cellular proliferation. In addition, this extract may promote dendritic cell (DC) maturation, increase interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) production, and may enhance natural killer (NK) cell activity, thus amplifying both innate and T cell-mediated immune responses against cancer cells. Check for active clinical trials or closed clinical trials using this agent.

A phase 2 trial exploring the effects of high-dose (10,000 IU/day) vitamin D(3) in breast cancer patients with bone metastases. Amir E, Simmons CE, Freedman OC, Dranitsaris G, Cole DE, Vieth R, Ooi WS, Clemons M. Cancer. 2009 Nov 13. [Epub ahead of print] PMID: 19918922 DOI: 10.1002/cncr.24749 METHODS: Patients with bone metastases treated with bisphosphonates were enrolled into this single-arm phase 2 study. Patients received 10,000 IU of vitamin D3 and 1000 mg of calcium supplementation each day for 4 months. The effect of this treatment on palliation, bone resorption markers, calcium metabolism, and toxicity were evaluated at baseline and monthly thereafter. CONCLUSIONS: Daily doses of 10,000 IU vitamin D3 for 4 months appear safe in patients without comorbid conditions causing hypersensitivity to vitamin D. Treatment reduced inappropriately elevated parathyroid hormone levels, presumably caused by long-term bisphosphonate use. There did not appear to be a significant palliative benefit nor any significant change in bone resorption. Cancer 2010. © 2009 American Cancer Society.

The National Cancer Institute is sponsoring a clinical trial of a new medicine in hopes that it will help mesothelioma patients whose cancers have been unresponsive to chemotherapy.

Impact of antioxidant supplementation on chemotherapeutic toxicity: a systematic review of the evidence from randomized controlled trials. Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C Int J Cancer. 2008 Sep 15;123(6):1227-39. Review. PMID: 18623084

Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Hoffer LJ, Levine M, Assouline S, Melnychuk D, Padayatty SJ, Rosadiuk K, Rousseau C, Robitaille L, Miller WH Jr. Ann Oncol. 2008 Nov;19(11):1969-74. Epub 2008 Jun 9. Erratum in: Ann Oncol. 2008 Dec;19(12):2095. PMID: 18544557 doi:10.1093/annonc/mdn377

Randomized trial of preoperative cimetidine in patients with colorectal carcinoma with quantitative assessment of tumor-associated lymphocytes. Kelly MD, King J, Cherian M, Dwerryhouse SJ, Finlay IG, Adams WJ, King DW, Lubowski DZ, Morris DL. Cancer. 1999 Apr 15;85(8):1658-63. PMID: 10223557

Effects of perioperative cimetidine administration on peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: results of a randomized controlled clinical trial. Li Y, Yang GL, Yuan HY, Bai DJ, Wang K, Lin CR, Hu MB, Feng MH. Hepatogastroenterology. 2005 Mar-Apr;52(62):504-8. PMID: 15816467

Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy: a randomized control trial. Gogos CA, Ginopoulos P, Salsa B, Apostolidou E, Zoumbos NC, Kalfarentzos F. Cancer. 1998 Jan 15;82(2):395-402. PMID: 9445198