This week I thought I'd share an interesting article from The Wall Street Journal discussing new research efforts to develop drugs that use the body’s own immune system to fight cancer.

Enlisting the Body to Fight Cancer
By THOMAS GRYTA

Scientists are scrambling to develop medications that fight cancer by spurring the body's immune system, a form of treatment that some cancer specialists believe may hold the key to keeping a patient permanently disease-free.

The new efforts come in the wake of recent Food and Drug Administration approvals of Dendreon Corp.'s Provenge, an immunotherapy drug used to treat prostate cancer, and Bristol-Myers Squibb Co.'s Yervoy, for melanoma.

Other immunotherapy drugs are being developed for a number of other cancers, including lung, brain and kidney cancers. Unlike most traditional therapies that attack a cancer directly, immunotherapy uses the body's own internal defenses to ward off the disease, with the ultimate hope of building up a long-term resistance to the cancer.

"If we are ever going to use the word 'cure', the immune system is going to have to come into play," says Stephen Hodi, director of the melanoma center at Dana-Farber Cancer Institute in Boston.

One of the ways that cancer survives and ultimately spreads through the body is by exploiting a function in all cells that prevents the immune system from killing them. Researchers have found that cancer cells have multiple methods of avoiding detection and suppressing the immune system's response.

"Why would cancer devote so much energy to avoid the immune system if the immune system didn't have the potential to reject the cancer?" says Robert Vonderheide from the Abramson Cancer Center of the University of Pennsylvania.

There are big hurdles to advancing the field of immunotherapy. Some of the drugs have significant side effects. And the complex treatments are among the priciest in health care. Yervoy costs about $120,000 for a course of treatment and Provenge $93,000.

The growing interest in immunotherapy comes even as traditional cancer-targeting drugs have become more effective. Still, such drugs often just delay the ultimate recurrence of the disease as tumors develop resistance to the treatment, or some cancer cells survive the therapy and regrow. The hope is that the immune system's long-term activity against the cancer could stop this cycle.

Varied Approaches

Immunotherapies can work in several ways. They can help the immune system increase its response so that it fights the cancer better; they can stop cancers from slowing down or halting the immune system's activation; or they can help the immune system find the tumor and kill it.

Provenge, which received FDA approval last year, is made by combining some of the patient's own immune cells with a specific protein that is created by most prostate cancers. Although the exact mechanism isn't fully understood, the drug, when given intravenously to the patient, is believed to activate other immune cells to see the cancer as a threat and attack it.

Yervoy is an antibody that binds to a molecule on certain immune-system cells that block them from becoming active. The addition of Yervoy allows the immune cells to become active and fight the cancer.

FDA approvals for Provenge and Yervoy helped set the stage for the current bout of drug research. "We don't have to convince people this is a good idea," says Ira Mellman, vice president of research oncology at Roche Holding AG's Genentech unit, which says it is developing immunotherapy drugs that target advanced solid tumors.

Bristol-Myers Squibb, maker of Yervoy, is investigating the drug's possible use for other cancers, including prostate and lung. And Dendreon is developing a drug for bladder cancer that works similarly to Provenge.

Other companies are also working on immunotherapy drugs. Roche Holding AG says its research is targeting advanced solid tumors, while GlaxoSmithKline PLC is focusing on several cancers, including lung and melanoma.

Among smaller pharmaceutical companies, Oncothyreon Inc. is working with Merck KGaA on a lung-cancer treatment, and Agenus Inc. is developing therapies in areas including brain cancer and kidney cancer.

There are currently 23 cancer immunotherapies in pipeline development, according to market-research firm Decision Resources.

The FDA currently limits Provenge and Yervoy to patients with advanced forms of their disease and with few other treatment options. Clinical trials have shown that Provenge has minimal side effects, but Yervoy can trigger immune-related reactions, which are fatal in some patients.

Side effects will continue to be heavily scrutinized as the drugs are expected to be used earlier in the disease progression or to prevent relapse.

Trial and Error

The idea of using the immune system first drew significant research attention in the mid- to late-1990s, but multiple failures led to widespread discouragement, says Dr. Vonderheide.

Developments in recent years have produced the momentum that researchers believe will allow it to reach the next level of more powerful treatments and, ultimately, their combination with both traditional drugs and other immunotherapies, he says.

Corrections & Amplifications
Bristol-Myers Squibb Co.'s Yervoy drug, used in treating melanoma, can trigger immune-related reactions, which are fatal in some patients. A previous version of this article incorrectly said Yervoy can trigger fatal allergic reactions in some patients.

Citation: Gryta, Thomas. “Enlisting the Body to Fight Cancer.” The Wall Street Journal, 14 June 2011, accessed 30 June 2011. http://online.wsj.com/article_email/SB10001424052702304778304576377892911572686-lMyQjAxMTAxMDIwOTEyNDkyWj.html

This week, Conversant Bio was graced with three bright interns for the summer – Bo Gilliam, Sara Grace Hastings, and Sam Barsh.

Bo is originally from Decatur, Alabama, a town about thirty minutes southwest of Huntsville. He has just completed his freshman year at Seton Hall University in South Orange, New Jersey. He is majoring in International Relations and wants to work in Sustainable Development/Micro Finance in China. In fact, to add to his future success in this arena, Bo is currently studying Chinese—a difficult language to learn, no doubt, but certainly a useful one. Bo is interning in Conversant Bio’s Sales and Marketing department.

Sara Grace, a Huntsville native, has just completed her junior year at Mississippi State University, where she is majoring in Biomedical Engineering. Her aspiration is to develop diagnostic machines. I gave her a puzzled look when she told me this, but she explained whereas companies like Conversant Bio work with scientists researching diagnostic genes, she wants to develop machines that diagnose. She is interning in my department—Data Management.

Originally from California’s Bay Area, Sam recently relocated with his family to Huntsville. He has just completed his freshman year at Stanford University, where his major is currently undecided, but he aspires to work in the medical field. I asked Sam what about the medical field attracted him. He replied, “I think it has a lot to do with growing up in an environment where both my parents were doctors and I could see the impact they made on people's lives. I enjoy learning about diseases and how the body works but that you can help people while doing that is what's most attractive about the field.” He sounds like a good candidate for medical field to me! Sam is also interning in Data Management.

Welcome, Interns! We’re happy to have you! We hope you learn at lot this summer!

One of the many ongoing discussions among scientists concerns the use of cell lines versus cells collected from actual patient tumors. Is one more accurate than the other? The following article gives us some insight into the debate.

How accurate are cancer cell lines?
Some argue that tumour cells obtained directly from patients are the best way to study cancer genomics.
Brendan Borrell

For decades, cancer cell cultures grown in Petri dishes have been the foundation of cancer biology and the quest for drug treatments. But now that biologists are exploring cancer genomes, some are asking whether they should pursue a more expensive, less proven strategy that may give a truer picture of key mutations: sequencing cells from tumours plucked directly from patients.

Of the first six cancer genome sequences to be published, three have come from established cell lines and three from primary tumours. Hundreds more sequences are expected soon, both from individual labs and from major efforts such as the Cancer Genome Atlas in Bethesda, Maryland. And although most researchers continue to have a foot in both camps, the atlas project excludes work on cell lines.

The major criticism of cell lines is that not all cancer types can be grown indefinitely in the laboratory. Those that do grow differ genetically from primary tissue, accumulating new mutations as they adapt to their artificial environment. When implanted in rodents, brain-cancer cell lines tend to form a 'bowling ball' mass of cells rather than infiltrating the brain like a spider web, as they do in humans, says Howard Fine, head of neuro-oncology at the National Institutes of Health in Bethesda. "The glioma [brain cancer] cell lines we've been using bear so little resemblance to what happens in people, it's no wonder that when we screen therapeutics on animals and bring them to the clinic they come back negative," he says.

Cell lines for other cancer types may resemble primary tumours more closely, but some teams still aren't interested. "To be honest, I'm not sure why you would ever want to sequence cell lines," says Timothy Graubert at Washington University in St Louis, Missouri. Graubert was an author on the first cancer genome to be published1, which was based on samples from a patient with acute myeloid leukaemia. "We feel the arguments in favour of using primary cells are compelling," he says.

But primary cells are more expensive to sequence because, unlike cell lines, they contain a mixture of genetically distinct cells, so researchers need to use costly techniques to pinpoint rare mutations that are not spread uniformly throughout the tumour. More crucially, says Stan Nelson, an oncologist at the University of California, Los Angeles, it will take thousands of comparisons between tumour sequences and normal DNA to equal the benefit of sequencing the top 100 cell lines, which are backed by a wealth of literature on their development and biology. And, so far, the results from genomic studies of primary tumours haven't impressed some cancer biologists. For example, most of the mutations that Graubert and his colleagues identified by comparing sequences from the tumour cells with normal tissue from the same individual turned out not to be significant, says Nelson. His group has sequenced the widely used glioma cell line U87MG (ref. 2), but he says there's value in both approaches.

Down but not out
This week, two studies in Nature3, 4 highlight the continued relevance of cell lines. Researchers led by pathologist Michael Stratton of the Wellcome Trust Sanger Institute in Cambridge, UK, analysed deletion mutations in 746 cell lines, including the 59 'NCI-60' lines that have been used in developing a wide range of cancer drugs3. Cell lines don't contain the non-cancerous cells found in primary tumours, making the cultivated lines ideal for finding deletions in the cancer genome, says Stratton. His group can then distinguish between segments of the genome that are lost as a result of breakage from those in which a tumour-suppressing gene has lost its functionality.

The second study, led by Matthew Meyerson of the Dana-Farber Cancer Institute in Boston, Massachusetts, searched for deletions and additions of chunks of DNA in 3,131 cancer specimens, including 541 cell lines. He says that the common alterations in cell lines, which include gains and losses of entire arms of chromosomes, are often the same ones found in primary tissue.

That's one reason why Meyerson takes a pragmatic view about the best way to study cancer genomes. Sequencing cancer cell lines makes sense in the short term, he says, but "millions and millions of people are getting cancer, and over time the statistical power of looking at primary tumours is going to be greater". This month, for instance, the Cancer Genome Atlas is shipping 200 colon-cancer samples to sequencing centres, one of 20 tumour types to be sequenced over the next five years.

References
1. Ley, T. J. et al. Nature 456, 66-72 (2008). | Article | PubMed | ChemPort |
2. Clark, M. J. et al. PLoS Genet. 6, e1000832 (2010). | Article | PubMed | ChemPort |
3. Bignell, G. R. et al. Nature 463, 893-898 (2010). | Article
4. Beroukhim, R. et al. Nature 463, 899-905 (2010). | Article

Citation: Borrell, Brendan. “How Accurate Are Cancer Cell LInes?” Nature News, 17 February 2010, accessed 8 June 2011, http://www.nature.com/news/2010/100217/full/463858a.html.

This week, I came across an article discussing the new hope researchers have in cancer treatments specific to gene mutations in tumors. As a company that often deals with client requests for blood and tissue samples from patients with specific gene mutations, Conversant Bio plays a key role in the research done in this area of cancer treatment. So I thought this would be a perfect article to share on the blog.

Success Seen with Personalized Cancer Treatment
By Deena Beasley

CHICAGO, June 3 (Reuters) - Tailoring cancer drugs to target the molecular signature of a tumor helps patients more than a scattershot approach, according to early-stage research.

The strategy is not an option for every type of cancer, but medical advances have led to the development of a number of drugs that target specific gene mutations in tumors, such as Roche's (ROG.VX: Quote, Profile, Research, Stock Buzz) Herceptin for a certain type of breast cancer or Gleevec, sold by Novartis (NOVN.VX: Quote, Profile, Research, Stock Buzz).

A phase 1 study conducted at the University of Texas MD Anderson Cancer Center found that matching therapies -- most still experimental -- to genetic markers led to higher rates of tumor shrinkage and survival in patients with advanced cancer.

The results were presented on Friday in Chicago at the annual meeting of the American Society of Clinical Oncology.

"The concept is quite simple ... we think you should match the abnormality with the targeted drug," said Dr. Razelle Kurzrock, professor and chair of MD Anderson's Department of Investigational Cancer Therapeutics.

The study involved 852 patients with cancer that was inoperable or had spread beyond the primary site. It found that 27 percent of the 175 patients with a single gene aberration who were treated with a matched drug had tumor shrinkage.

The response rate was 5 percent in the 438 patients without an aberration. The other patients -- who were treated with drugs that did not match their genetic mutations -- had a response rate of 8 percent.

Median survival was 15.8 months for patients with one mutation who were treated with a matched drug, compared with 9.7 months for those patients who were not matched to a targeted therapy.

Dr. Kurzrock said use of molecular testing for cancer patients is not yet standard clinical practice, although it is becoming more common as new drugs are approved and testing is made available.

Since the signing of the National Cancer Act 40 years ago, the average five-year survival rate for all U.S. cancer patients has risen by 18 percent, according to ASCO.

That has been due largely to improvements in traditional chemotherapy drugs, which work by interfering with the entire body's system of cell replication, causing harsh side effects like nausea, hair loss and fatigue.

Newer targeted drugs, made possible by the decoding of the human genome, aim to block specific pathways that cancer cells use to grow and reproduce. The list of targets is an alphabet soup of genes such as PIK3CA, mTOR, MEK, EGFR, RET and BRAF.

Elaine Silk, 54, was diagnosed nine years ago with melanoma, a deadly form of skin cancer.

She has endured numerous surgeries and drug regimens -- including a round of immune boosters that required hospitalization and caused her brain to swell -- but considers herself cancer-free after a year of treatment with an experimental BRAF-blocking drug.

"There are a few side effects, but nothing like before ... my hair is really curly," said Silk, who lives in rural Texas. "I take three pills twice a day ... I look at it like medication for high blood pressure that keeps the disease under control."

Dr. Kurzrock said more work is needed since the MD Anderson study was an analysis of retrospective data, rather than a randomized trial.

She also said it would make sense to match targeted therapies to patients with earlier-stage cancer.

Citation: Beasley, Deena. “Success Seen with Personalized Cancer Treatment.” Reuters, June 3, 2011, accessed June 3, 2011,
http://www.reuters.com/article/2011/06/03/cancer-mutations-idUSN0314914120110603.

With Memorial Day ahead, some of us here at Conversant are taking advantage of the extended weekend to finally use PTO, turning the weekend into a week-long vacation. The rest of us are simply using the extra day to grill, relax, enjoy friends, or just catch up on sleep (my personal preference). No matter how we plan to spend it though, the goal is to come back rested and refreshed. We hope you do the same.

From all of us, Happy Memorial Day!

Conversant Bio Value #3: Quality with Urgency

The list below represents surgical cases happening next week (week of 5.23.11) in our clinics.  If you need fresh tumor tissue delivered to you within 24 hours of resection please contact us.  All samples are shipped refrigerated in HypoThermosol.

Cancer Types  -  # Still Available (Total for Week)
Breast Cancer  -  5 (6)
Colorectal  -  1 (4)
Non-Small Cell Lung  -  1 (12)
Prostate  -  0 (1)
Ovarian  -  1 (3)
Renal  -  0 (1)
GBM  - 1 (2)
Uterine  -  0 (1)
Melanoma -  0 (1)
TOTAL  -  9 (31)

Contact us any time for ordering FRESH Whole Blood from oncology, hematology, and auto-immune patients.

Because patients are waiting,
Conversant Bio

___
On The Web:
www.conversantbio.com
www.twitter.com/conversantbio
www.youtube.com/conversantbio
www.conversantbio.com/blog (latest Forward Calendar details)
___
Available Formats:
Fresh / Flash Frozen / FFPE + Matched Blood.
___
Uses:
Xenografts, Drug Testing, Creating FFPE Repository, Dissociation to Cells, among many other things.
___
Order Today:
East Coast U.S. = Christine Aubin, (781) 715-5703, christine.aubin@conversantbio.com
West Coast U.S. = Dan Searson, (858) 225-2923, dan.searson@conversantbio.com
Europe = Markus Gemein, markus.gemein@cellsystems.de
Japan = Keiichi Yokoyama, k.yokoyama@ontarget-ddss.co.jp
___
Opt-out by emailing me any time.  Thank you, Luke.

Here at Conversant, when we make an accomplishment--whether company-related or personal--we not only like to announce it during our weekly team update meeting, but we also have a tradition of ringing a bright, Conversant-orange cowbell. Exclusive to Conversant, this cowbell is reserved for significant accomplishments within the team, and when rung, it signifies the team's praise as we recognize that accomplishment.

This week, there were three reasons we rang the cowbell:

--First, congrats to the lab’s Oke Ebenezar for graduating last Friday from Alabama A&M University. She graduated Summa Cum Laude, earning a Masters of Science with a concentration in physiology. Admit it, Oke, you’re a genius.

--Second, congrats to accounting's Cassandra Escue for getting her braces off last Tuesday. Finally, you can bite into apples with reckless abandon!

--And third, if I may be so bold, congrats to me for passing the GRE last Saturday. Can I get a "woot, woot!"

Congratulations, Team!

Everything we do as a Company, we do because patients are waiting.  The list below represents surgical cases happening next week (week of 5.16.11) in our clinics.  If you need fresh tumor tissue delivered to you within 24 hours of resection please contact us.  All samples are shipped refrigerated in HypoThermosol.

Cancer Types  -  # Still Available (Total for Week)
Breast Cancer  -  6  (8)
Colorectal  -  4  (5)
Non-Small Cell Lung  -  3  (6)
Prostate  -  0  (2)
Ovarian  -  4  (5)
Renal  -  1  (2)
GBM  -  2  (3)
Uterine  -  2  (4)
Melanoma -  1  (3)
TOTAL  -  23   (38)

Contact us any time for ordering FRESH Whole Blood from oncology, hematology, and auto-immune patients.

Because patients are waiting,
Conversant Bio

___
On The Web:
www.conversantbio.com
www.twitter.com/conversantbio
www.youtube.com/conversantbio
www.conversantbio.com/blog (latest Forward Calendar details)
___
Available Formats:
Fresh / Flash Frozen / FFPE + Matched Blood.
___
Uses:
Xenografts, Drug Testing, Creating FFPE Repository, Dissociation to Cells, among many other things.
___
Order Today:
East Coast = Christine Aubin, (781) 715-5703, christine.aubin@conversantbio.com
West Coast = Dan Searson, (858) 225-2923, dan.searson@conversantbio.com
___
Opt-out by emailing me any time.  Thank you, Luke.

As I sat ritually drinking my morning cup of coffee and browsing through the latest headlines in Google News, I came across an article announcing a new study linking coffee consumption to breast cancer treatment. Being a regular coffee drinker myself, and female, I had to read the article. I found it quite interesting and thought you would too.

Are Coffee Drinkers Less Prone to Aggressive Breast Cancer?
Study sees lower risk for ER-negative tumors, which don't respond to hormonal therapies
By Alan Mozes
HealthDay Reporter

TUESDAY, May 10 (HealthDay News) -- Women who drink a substantial amount of coffee each day may lower their risk for developing a particular type of breast cancer, Swedish researchers say.

Their study linked consumption of five or more cups of coffee a day to a relatively marked reduction in the non-hormone-responsive disease known as ER-negative breast cancer. However, coffee consumption did not appear to lower the risk for developing ER-positive breast cancer, a hormone-responsive estrogen receptor form of the disease.

Daily consumption of coffee may protect against the most aggressive type of breast cancer, ER-negative, said study co-author Dr. Per Hal, a professor in the medical epidemiology and biostatistics department at the Karolinska Institute in Stockholm.

"Now, we don't have all the details," he cautioned. "We don't know, for example, what specific type of coffee we're talking about here. But what we do know is that the protective effect is quite striking and remains even after adjusting for a lot of other factors that have the potential to play a protective role. And we know that we're talking about what we could call a relatively normal amount of coffee drinking. Certainly we're not talking about consuming gigantic amounts of coffee. So, this is a very intriguing finding."

The study, reported online May 11 in Breast Cancer Research, involved 5,929 Swedish women, aged 50 to 74. About half of the women had breast cancer.

Questionnaires were used to assess behavioral and health characteristics, including smoking and drinking patterns, physical activity routines, family history of breast cancer, hormone therapy protocols, nutritional intake, body mass index, education level and coffee consumption habits. Both tumor status and breast cancer type were also noted.

The principle finding: Drinking coffee appeared to spur a "strong reduction" in risk for ER-negative breast cancer, the researchers wrote. Women who drank five cups of coffee a day had a 33 percent to 57 percent lower risk for ER-negative cancer than did those who drank less than one cup a day.

The study revealed an apparent association between coffee consumption and a reduction in breast cancer risk, but not a cause-and-effect relationship.

And Hal was not eager for consumers to jump to conclusions.

"There are one or two other studies that have pointed in the same direction as ours -- but not many, just a few," he cautioned. "So before I would go to tell my neighbors to start drinking more coffee than they already do, I would like to know what is the biological mechanism at work here. And that's not yet clear."

Hal noted that he and his colleagues are now working on a new study to tease out that information.

Dr. Stephanie Bernik, chief of surgical oncology at Lenox Hill Hospital in New York City, described the findings as both "interesting" and "provocative," given that the kind of cancer coffee appears to protect against is one for which there are relatively few effective treatments.

"It is this kind of study that opens the door to improving treatment, as scientists try to uncover what biologic factors in a substance are beneficial, and then attempt to extract these factors and use them to defend against cancers," Bernik noted. "The goal would be to try and discover what it is in coffee that may be beneficial."

"The next step is to find out what chemical factors in coffee cause the decreased rate of cancer and then attempt to see if these same chemicals can be used to treat a patient once they are already diagnosed with cancer," she said.

Citation: Mozes, Alan. “Are Coffee Drinkers Less Prone to Aggressive Breast Cancer?,” U.S. News & World Report, May 11, 2011, accessed May 11, 2011, http://health.usnews.com/health-news/family-health/cancer/articles/2011/05/11/are-coffee-drinkers-less-prone-to-aggressive-breast-cancer.

Congratulations, Team!