Gene identified in 10% of multiple myeloma cases

Combining the number-crunching potency of computers with an exploration of the genetic code, scientists have identified a new master gene in cancer.

The research, published by separate teams in the journal Nature Genetics, could open up avenues to identify people at risk and, potentially, new drugs to block the mechanisms that let cancers proliferate, they hope.

British-based researchers said a gene called UTX, found in the X gender chromosome, played the role of ringmaster in 10 percent of cases of multiple myeloma and one in 12 cancers of the oesophagus.

UTX controls an enzyme that contributes to the structure of DNA in our cells. The enzyme also acts as a switch, turning other genes on and off.

In a massive genetic trawl through tissue samples from patients with a form of kidney cancer, the scientists found a rare but telling signature among a mutated form of UTX.

By expanding the search to other cancer types, they also found the variant gene played a part in multiple myeloma -- cancer of the immune cells -- and in throat tumours.

"It influences some of the most fundamental mechanisms controlling gene activity in our cells," said Andy Futreal, co-leader of the Cancer Genome Project at Britain's Wellcome Trust Sanger Institute, which led the study.

"Unlike many cancer genes, UTX does not appear to be directly involved in cell division or cell death but in basic regulation, and shows the depths to which cancers will plumb in order to get themselves ready to go."

Biomarkers for Drug Effectiveness

Micromedic Technologies Ltd. has found two successes in a preliminary trial together with the University of Florida for the development of innovative biomarkers for pharmacogentics, the improvement of drug effectiveness. The trial tested 47 patients with multiple myeloma receiving Aredia and Zometa.

The trial objective was to test whether the use of Micromedic's genetic biomarker could predict which patients will develop side effects from the drugs; namely significant deterioration in bones of the mouth. Currently, 13% of multiple myeloma patients receiving these two drugs develop this side effect.

Professor Joseph Katz, Director of the University of Florida's College of Dentistry, Department of Oral Diagnostic Science oversaw the trial. Micromedic's genetic biomarker found a group of patients that were 11.6 times more likely to develop the side effects, compared with the control group. Micromedic's goal is for its test to be conducted on every patient who is a candidate for the drugs, so that patients who are predicted to develop the side effect can be given alternative treatment or be given treatments in advance to prevent the side effect.

Micromedic will now conduct a further trial to confirm the findings.

BioKine $1.2M grant for new BKT140 drug

Biokine Therapeutics, Ltd. has received a $1.2 million research grant to support a Phase I/IIa clinical study to test the safety and the efficacy of the company’s flagship product, cancer drug BKT140.

In experimental models of chemotherapy treatments and bone-marrow transplants BKT140 caused the death of myeloma and leukemia cells, while encouraging the production of normal cells.

BioKine founder and CEO Dr. Amnon Peled said, “This is an exciting and significant time for the scientists, development staff, and investors who have supported the project. It is our goal to help cure and relieve the suffering of those struck by this cruel disease. Early data indicates that BKT140 may help us realize this goal."

Biokine develops pharmaceuticals that control the activity of receptors for molecules called chemokines, which play a key role in the development of cancer and inflammatory diseases.

Novel Agents and Multiple Myeloma

Improved survival of patients with multiple myeloma after the introduction of novel agents and the applicability of the International Staging System (ISS): an analysis of the Greek Myeloma Study Group (GMSG).

Kastritis E, Zervas K, Symeonidis A, Terpos E, Delimbassi S, Anagnostopoulos N, Michali E, Zomas A, Katodritou E, Gika D, Pouli A, Christoulas D, Roussou M, Kartasis Z, Economopoulos T, Dimopoulos MA.

1Department of Clinical Therapeutics, Alexandra Hospital, University of Athens School of Medicine, Athens, Greece.

When the novel agents thalidomide, bortezomib and lenalidomide are administered to patients with myeloma in the context of clinical trials, they are associated with a significant improvement in response, progression-free survival and in some studies, overall survival (OS); however, their effect on the outcome of unselected myeloma patients has not been fully assessed. We compared the outcome of 1376 unselected patients with symptomatic myeloma, who started treatment before or after the introduction of thalidomide. The median OS in patients who started treatment after the introduction of novel agents increased by 12 months (48 vs 36 months, P<0.001).>70 years (from 26 to 33 months, P=0.27). In patients treated after the introduction of novel agents, the international staging system (ISS) could discriminate three groups with significantly different outcomes (5-year survival for ISS stage I, II and III was 66, 45 and 18%, respectively, P<0.001). ISS was also valid in patients who actually received upfront treatment with novel drugs (4-year survival rate was 85, 61 and 26% for ISS stage I, II and III patients, P=0.001).Leukemia advance online publication, 19 February 2009; doi:10.1038/leu.2008.402.

PMID: 19225533 [PubMed - as supplied by publisher]

Green tea polyphenols block the anticancer effects of bortezomib

Golden EB, Lam PY, Kardosh A, Gaffney KJ, Cadenas E, Louie SG, Petasis NA, Chen TC, Schonthal AH.

Department of Pathology, University of Southern California (USC) Keck School of Medicine (KSOM), Los Angeles, CA, United States.

The anticancer potency of green tea and its individual components is being intensely investigated, and some cancer patients already self-medicate with this 'miracle herb' in hopes of augmenting the anticancer outcome of their chemotherapy. Bortezomib (Velcade((R))) is a proteasome inhibitor in clinical use for multiple myeloma. Here, we investigated whether the combination of these compounds would yield increased antitumor efficacy in multiple myeloma and glioblastoma cell lines in vitro and in vivo. Unexpectedly, we discovered that various green tea constituents, in particular (-)-epigallocatechin gallate (EGCG) and other polyphenols with 1,2-benzenediol moieties, effectively prevented tumor cell death induced by bortezomib in vitro and in vivo. This pronounced antagonistic function of EGCG was only evident with boronic acid-based proteasome inhibitors (bortezomib, MG-262, PS-IX), but not with several non-boronic acid proteasome inhibitors (MG-132, PS-I, nelfinavir). EGCG directly reacted with bortezomib and blocked its proteasome inhibitory function; as a consequence, bortezomib could not trigger endoplasmic reticulum stress or caspase-7 activation, and did not induce tumor cell death. Taken together, our results indicate that green tea polyphenols may have the potential to negate the therapeutic efficacy of bortezomib and suggest that consumption of green tea products may be contraindicated during cancer therapy with bortezomib.

PMID: 19190249 [PubMed - as supplied by publisher]

MMRF and LLS Fund $500,000 In Cancer Stem Cell Research

The Multiple Myeloma Research Foundation (MMRF) and the Leukemia & Lymphoma Society (LLS) have partnered to award William Matsui, MD, Johns Hopkins University, and Irving Weissman, MD, Stanford University, research grants totaling $500,000 to study the multiple myeloma cancer stem cell. Each individual grant is valued at $250,000.

These grants, developed in response to input from leading cancer stem cell experts who participated in the 2008 MMRF Myeloma Cancer Stem Cell Research Roundtable, provide an unprecedented opportunity to apply existing knowledge of cancer stem cells to multiple myeloma.

Ultimately, the identification and characterization of the multiple myeloma cancer stem cell will advance our understanding of drug resistance and relapse in patients with multiple myeloma and potentially lead to the development of targeted therapies that effectively treat the disease. Many researchers believe that cancer stem cells, although few in number, are responsible for cancer's development, metastases, and recurrence.

About Multiple Myeloma: Multiple myeloma is an incurable cancer of the plasma cell. The five-year relative survival rate for multiple myeloma is approximately 35%, one of the lowest of all cancers. In 2008, an estimated 19,920 adults (11,190 men and 8,730 women) in the United States were diagnosed with multiple myeloma and an estimated 10,690 people died from the disease.

Alcohol increases cancer risk in women in UK

A glass of wine each evening is enough to increase your risk of developing cancer, women are being warned.

Consuming just one drink a day causes an extra 7,000 cancer cases - mostly breast cancer - in UK women each year, Cancer Research UK scientists say.

The risk goes up the more you drink, whether spirits, wine or beer, the data on over a million women suggests.

Overall, alcohol is to blame for about 13% of breast, liver, rectum, mouth and throat cancers, the researchers say.

They estimate that about 5,000 cases of breast cancer in the UK - 11% of the 45,000 cases diagnosed each year - can be attributed to women's consumption of alcohol.

The study looked specifically at women who consumed low to moderate levels of alcohol - defined as three drinks a day or fewer.

Over the seven years of the study, published in the Journal of the National Cancer Institute, a quarter of the 1.3 million women reported drinking no alcohol.

Of those who did drink, virtually all consumed fewer than 21 drinks per week, and an average of 10g of alcohol per day, which is equivalent to just over one unit of alcohol found in half a pint of lager, a 125 ml glass of wine or a single measure of spirits.

Nearly 70,000 of the middle-aged women developed cancer and a pattern emerged with alcohol consumption.

Consuming one drink a day increased the risk of all types of cancer by 6% in women up to the age of 75.

The rates for individual cancers varied, with one drink a day causing a 12% rise in the risk of breast cancer, a 10% rise in rectal cancer, a 22% rise in gullet cancer, a 29% rise in mouth cancer and a 44% rise in throat cancer.

On a population scale, this would mean 15 extra cases of these cancers diagnosed for every 1,000 women - comprising 11 breast, one mouth, one rectal cancer and 0.7 each for cancers of the gullet, throat and liver.
Breast cancer is now the most common cancer in the UK. Each year almost 45,000 women are diagnosed with breast cancer. A woman's lifetime risk for breast cancer in the UK is one in nine.

Source: http://news.bbc.co.uk/go/pr/fr/-/1/hi/health/7906355.stm