Posts Tagged ‘australia’

New ways to treat solid tumors using protein

As EphA3 is present in normal organs only during embryonic development but is expressed in blood cancers and in solid tumors, this antibody-based approach may be a suitable candidate treatment for solid tumors.

The researchers from Monash University and Ludwig Cancer Research, in Australia, and KaloBios Pharmaceuticals, in the US, have had their findings published in the journal Cancer Research.

The team, led jointly by the late Professor Martin Lackmann, from the School of Biomedical Sciences at Monash; and Professor Andrew Scott, from Ludwig Cancer Research, has found that even if tumor cells do not have this molecule they can thrive by recruiting and taking advantage of supporting EphA3-containing cells in the tumor micro-environment.

First author, Dr Mary Vail, Monash Department of Biochemistry and Molecular Biology said: “The tumor cells send out signals to the surrounding area and say: ‘We need a blood supply and a foundation upon which to spread’.”

“We have shown that EphA3 expressing stromal stem cells, which are produced by the bone marrow, form cells that support and create blood vessels in tumors,” Dr Vail said.

Professor Andrew Scott’s team at Ludwig introduced human prostate cancer cells into a mouse model to mimic disease progression in humans. EphA3 was found in stromal cells and blood vessels surrounding the tumor.

They also observed that treatment with an antibody against EphA3 (chIIIA4) significantly slowed tumor growth. The antibody damaged tumor blood vessels and disrupted the stromal micro-environment, and cancer cells died because their ‘life-support’ was compromised.

“In addition, we screened various tumors from patient biopsies — sarcomas, melanomas as well as prostate, colon, breast, brain and lung cancers — and confirmed EphA3 expression on stromal cells and newly forming blood vessels,” Professor Scott said.

“Our research findings indicate that the tumor micro-environment is important, and monoclonal antibodies against EphA3 are one way to target and kill a variety of solid tumors as well as blood cancers.”

Currently, KaloBios Pharmaceuticals is testing the anti-EphA3 antibody KB004 in a multi-centre Phase I/II clinical trial in Melbourne and the US in patients with EphA3 expressing blood malignancies: AML, MDS and myelofibrosis.

Dr Vail, who collaborated with her former mentor on the project for 10 years, said this research represented Martin Lackmann’s life work.

“Martin was dedicated to helping people, and believed that KB004 was a promising therapeutic approach. He rightly anticipated that it would be well-tolerated in cancer patients, and through this collaborative project, his pioneering research has progressed to clinical trials and potentially new treatments for cancer patients,” Dr Vail said.

source : http://www.sciencedaily.com/releases/2014/08/140815102231.htm

New genetic risk markers in pancreatic cancer

The markers are variations in the inherited DNA code at particular locations along chromosomes. Several of these variations in the DNA code were identified that influence an individual’s risk for pancreatic cancer.

The discovery of these markers — along with four that were previously identified is important for several reasons, said Brian Wolpin, MD, MPH, first author of the report published online by Nature Genetics. One is that further study of these DNA variants may help explain on the molecular level why some people are more or less susceptible to pancreatic cancer than the average person. A second is the potential to identify people at increased risk who then might be candidates to undergo MRI or ultrasound scanning to look for early, treatable pancreatic tumors.

“Currently there is no population screening program for pancreatic cancer, which in 80 percent of cases is discovered when it’s too late to allow curative surgery — the cancer has already spread,” said Wolpin.

The only healthy individuals currently screened for pancreatic cancer are members of high risk families due to multiple family members with pancreatic cancer. “But the field has been struggling to find factors that can identify people at highest risk in the general population, when a strong family history is not present,” Wolpin said.

The study findings represent analyses of DNA from 7,683 patients with pancreatic cancer and 14,397 control patients without this cancer, all of European descent, from the United States, Europe, Canada, and Australia. The scientists used sequencing technology to examine more than 700,000 sites of the genome known to have single nucleotide polymorphisms (SNPs) — differing versions of a single letter of DNA code. These variations can alter the expression of a gene or the content of its message, and the researchers looked for variants that were associated with the risk of having pancreatic cancer. Research of this type is called a genome-wide association study, or GWAS.

Wolpin said the results confirmed the presence of four risk-associated SNPs that had been identified in a previous, smaller GWAS study. In addition, five new risk markers were discovered and a sixth that was of borderline statistical significance.

The risks linked to each SNP or marker were largely independent and additive, so that they may have utility in future attempts to identify individuals in the general population at higher risk for pancreatic cancer. The average lifetime risk of pancreatic cancer is 1.5 percent.

The long-term goal is to create a “risk stratification tool” that could be used in primary care practice to identify individuals who should undergo screening for pancreatic cancer with tests such as ultrasound or MRI.

The report includes authors from around the world, and includes several senior authors, one of whom is Charles Fuchs, MD, MPH, of Dana-Farber.

The project, known as PanScan III, was funded by numerous sources, including the National Cancer Institute of the National Institutes of Health under contract number HHSN261200800001E and the Lustgarten Foundation.

source : http://www.sciencedaily.com/releases/2014/08/140803193131.htm