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June 12, 2009

Cancer Breakthroughs : Unraveling Genetic Sequences for Cancer Cures, Ultrasound/Magnets for Zapping Tumors, 2-in-1 Breast Cancer Treatment and More

1. Colorectal cancer is especially difficult to diagnose in its early stages - usually, people are in advanced stages when the cancer is discovered, and the diagnostic process itself requires the removal of entire polyps as well as a laboratory assessment that may take weeks.

Vernick's [ doctoral student of the Department of Physical Electronics at Tel Aviv University] lab-on-a-chip solution works by recognizing tell-tale biomarkers that lab technicians cannot see with the naked eye. Cancer biomarkers are molecular changes detectable in the tumor or in the blood, urine, or other body fluids of cancer patients. These biomarkers are produced either by the tumor itself or by the body in response to the presence of cancer. The most commonly-used biomarker tests used today are the off-the-shelf pregnancy test and the test used by diabetics to monitor blood-sugar levels.



With his tool, Vernick can scan up to four different biomarkers for colon cancer, an extraordinarily effective method for finding elusive colon cancer malignancies.

The chip is essentially an electrochemical biosensor programmed to recognize and bind to colorectal cancer biomarkers with high specificity. "Following this bio-recognition event, the electrodes on the chip transduce the signal it receives into an electric current, which can be easily measured and quantified by us," says Vernick.

In addition to the lab-on-a-chip technology, Vernick and his fellow researchers believe they are well on the way to establishing a blood test for colon cancer, which, when used together with colonoscopies, offers a comprehensive package of colon cancer detection.

"When you combine all these methods together, you increase the level of confidence in the results, eliminating false positives and negatives which are dominant today in tests for colorectal cancer," says Vernick. This research, which is funded in part by American-Israeli businessman and philanthropist Lester Crown, is to be commercialized as a complete method of cancer detection, combining blood screening and biopsy.

The ultimate goal would be for patients to have the ability to test themselves at home. "Glucose sensors used by diabetics are the best example today of a hand-held home biosensor test," says Vernick. In the future, he would like to offer patients a similar technology for colorectal cancer detection, in partnership with their physicians. "A person could submit the results of a home test directly online or to their doctor. This is my ultimate goal," he says.


2. BC Cancer Agency and Vancouver Coastal Health Research Institute, discovered that a single genetic mutation is responsible for granulosa cell tumours, which are a rare and often untreatable form of ovarian cancer.



The discovery is akin to finding a needle in a haystack, as there are three billion components to the genetic code of the tumour.

The research, published this week in the New England Journal of Medicine, can be applied to more than ovarian cancer. The use of state-of-the-art technology to identify the single mutation in ovarian cancer's DNA means the same technology can be used to unravel the genetic sequences of other cancers The breakthrough cancer discovery that has potential to lead to a host of new cancer diagnostics and treatments. The ability to decode the genetic sequences of specific cancers will be part of a road map to truly personalized medicine, in which doctors will be able to come up with an individualized "recipe" for every patient.

Mutation of FOXL2 in Granulosa-Cell Tumors of the Ovary [New England Journal of Medicine]



Full text of the ovarian cancer discovery paper

32 page supplemental pdf

3. Friedward Winterberg (major researcher in nuclear fusion and for the ideas that led to the global positioning system) has proposed to treat cancer by the combination of a strong magnetic field with intense ultrasound. At the low electrical conductivity of tissue the magnetic field is not frozen into the tissue, and oscillates against the tissue which is brought into rapid oscillation by the ultrasound. As a result, a rapidly oscillating electric field is induced in the tissue, strong enough to disrupt cancer cell replication. Unlike radio frequency waves, which have been proposed for this purpose, ultrasound can be easily focused onto the regions to be treated. This method has the potential for the complete eradication of the tumor. [H/T Joel Campbell, NASA]






4. Scientists from the Breakthrough Breast Cancer Research Centre based at the Institute of Cancer Research have shown for the first time that it is possible for one drug to simultaneously attack cancer cells in two completely different ways. Researchers now hope this discovery could lead to further two-in-one treatments - meaning breast cancer patients could potentially need to take fewer drugs to treat tumours in the future.

The team showed that an experimental compound called PTK/ZK, originally developed as an 'angiogenesis inhibitor' to block a tumour's blood supply and slow its growth, also acted as an 'aromatase inhibitor'. In this way it prevents the growth of hormone sensitive breast cancers reliant on oestrogen for their growth and survival. This type of breast cancer accounts for over 70% of all cases of breast cancer.


5. A team of scientists claims to have developed a drug capable of treating skin cancer even in its most-advanced stages.

Presenting their findings at a meeting of the American Society of Clinical Oncology in Florida, researchers from Roche and Plexxikon explained that the drug PLX4032, which is still in its experimental stages, could work to combat malignant melanomas.

6. Researchers at McGill University and the University of Pennsylvania have discovered that a widely used anti-diabetic drug can boost the immune system and increase the potency of vaccines and cancer treatments. Their findings will be published June 3 in the journal Nature.

Few talk about cancer and diabetes in the same breath. However, recent advances have uncovered common links between cancer and diabetes, in particular how metabolic pathways, the basic chemical reactions that happen in our cells, are controlled in these diseases. The recent findings suggest a new link between the metabolic pathways deregulated in cancer and diabetes and their role in immune cell function. The results suggest that common diabetic therapies which alter cellular metabolism may enhance T-cell memory, providing a boost to the immune system. This could lead to novel strategies for vaccine and anti-cancer therapies.


7. University of Florida researchers have come up with a new gene therapy method to disrupt cancer growth by using a synthetic protein to induce blood clotting that cuts off a tumor's blood and nutrient supply.

In mice implanted with human colorectal cancer cells, tumor volume decreased 53 percent and cancer cell growth slowed by 49 percent in those treated with a gene that encodes for the artificial protein, compared with those that were untreated.


8. MicroRNA Replacement Therapy May Stop Cancer In Its Tracks

Scientists at Johns Hopkins have discovered a potential strategy for cancer therapy by focusing on what's missing in tumors. They have discovered a potential strategy for cancer therapy by focusing on what's missing in tumors. A new study suggests that delivering small RNAs, known as microRNAs, to cancer cells could help to stop the disease in its tracks. MicroRNAs control gene expression and are commonly lost in cancerous tumors.

Publishing results of the study June 12 in Cell, the researchers say they have provided one of the first demonstrations that microRNA replacement provides an effective therapy in an animal model of human disease.

"This work suggests that microRNA replacement may be a highly effective and nontoxic treatment strategy for some cancers or even other diseases," says Josh Mendell, M.D., Ph.D., an associate professor in the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine. "We set out to learn whether tumors in a mouse model of liver cancer had reduced levels of specific microRNAs and to determine the effects of restoring normal levels of these microRNAs to these cancer cells. We were very excited to see that the tumors were, in fact, very vulnerable to microRNA replacement."


9. Cancer detection progress from the Canary Foundation. Article by Melanie Swan.

The Canary Foundation’s annual symposium held May 4-6, 2009 indicated progress in two dimensions of a systemic approach to cancer detection: blood biomarker identification and molecular imaging analysis.

Systems approach to cancer detection
A systems approach is required for effective cancer detection as assays show that many proteins, miRNAs, gene variants and other biomarkers found in cancer are also present in healthy organisms. The two current methods are one, looking comprehensively at the full suite of genes and proteins, checking for over-expression, under-expression, mutation, quantity, proximity and other factors in a tapestry of biological interactions and two, seeking to identify biomarkers that are truly unique to cancer, for example resulting from post-translational modifications like glycosylation and phosphorylation. Establishing mathematical simulation models has also been an important step in identifying baseline normal variation, treatment windows and cost trade-offs.

Blood biomarker analysis
There are several innovative approaches to blood biomarker analysis including blood-based protein-assays (identifying and quantifying novel proteins related to cancer), methylation analysis (looking at abnormal methylation as a cancer biomarker) and miRNA biomarker studies (distinguishing miRNAs which originated from tumors). Creating antibodies and assays for better discovery is also advancing particularly protein detection approaches using zero, one and two antibodies.

Molecular Imaging
The techniques for imaging have been improving to molecular level resolution. It is becoming possible to dial-in to any set of 3D coordinates in the body with high-frequency, increase the temperature and destroy only that area of tissue. Three molecular imaging technologies appear especially promising: targeted microbubble ultrasound imaging (where targeted proteins attach to cancer cells and microbubbles are attached to the proteins which make the cancerous cells visible via ultrasound; a 10-20x cheaper technology than the CT scan alternative), Raman spectroscopy (adding light-based imaging to endoscopes) and a new imaging strategy using photoacoustics (light in/sound out).

Tools: Cancer Genome Atlas and nextgen sequencing
As with other high-growth science and technology areas, tools and research findings evolve in lockstep. The next generation of tools for cancer detection includes a vast cataloging of baseline and abnormal data and a more detailed level of assaying and sequencing. In the U.S., the NIH’s Cancer Genome Atlas is completing a pilot phase and being expanded to include 50 tumor types (vs. the pilot phase’s three types: glioblastoma, ovarian and lung) and abnormalities in 25,000 tumors. The project performs a whole genomic scan of cancer tumors, analyzing mutations, methylation, coordination, pathways, copy number, miRNAs and expression. A key tool is sequencing technology itself which is starting to broaden out from basic genomic scanning to targeted sequencing, whole RNA sequencing, methylome sequencing, histone modification sequencing, DNA methylation by arrays and RNA analysis by arrays. The next level would be including another layer of detail, areas such as acetylation and phosphorylation

Future paradigm shifts: prevention, omnisequencing, nanoscience and synthetic biology
Only small percentages of annual cancer research budgets are spent on detection vs. treatment, but it is possible that the focus will be further upstreamed to prevention and health maintenance as more is understood about the disease mechanisms of cancer. Life sciences technology is not just moving at Moore’s Law paces but there are probably also some paradigm shifts coming.



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