Cancer breakthroughs often get their first airing at the annual meeting of the American Society of Clinical Oncology. This year’s meeting was no exception.

One finding getting a lot of press has its origins in a pair of studies in Nature in 2005. The studies showed how to selectively kill cancer cells deficient in BRCA1 and BRCA2, genes that are mutated in some of the deadliest breast and ovarian cancers.

The agent that does the killing is called a PARP inhibitor. And trial results released last week show some pretty promising results.

Olaparib, a PARP inhibitor under development by AstraZeneca PLC, shrank tumors in more than a third of women whose breast cancers had BRCA mutations. The trial did not have a control arm, but the data look encouraging, considering the agent was given alone, without other drugs, and that the subjects had already had an average of 3 chemotherapy regimens. A similar trial showed that the drug could also shrink advanced ovarian tumors in subjects with BRCA1 or BRCA2 mutations.

A truer test of whether a drug is likely to help patients is whether it can prolong survival. A randomized, controlled trial of BS1-201, under development by Sanofi-Aventis SA, examined this question in 116 women with some pretty nasty tumors: their breast cancer had metastasized to other parts of their body and was ‘triple negative’, meaning it lacked receptors on their tumors for estrogen, progesterone and HER2, each of which are targets for current therapies. The drug prolonged survival by three and a half months, to 9.2 months, when added to a standard chemotherapy regimen.

Bigger studies are needed, but the findings so far validate a concept with deep origins in basic research. BRCA1 and BRCA2 facilitate DNA repair, a function that emerged after years of painstaking research. PARP (poly(ADP)-ribose polymerase) mediates DNA repair also, but in a distinct way. The Nature studies exposed cells lacking BRCA1 or BRCA2 to PARP inhibitors and showed that these cells get nailed: their DNA is such a fragmented mess that they die.

Mice deficient in PARP are viable, fertile and tumor-free, which bodes well for the side effect profile of these drugs. Subjects who received the drugs reported only mild side effects, including nausea and fatigue.

Other highlights at ASCO include promising findings with multikinase inhibitors, which can block several types of proteins that go astray in tumor cells. Cancer vaccine approaches also got a boost with positive findings from trials in melanoma and non-Hodgkin’s lymphoma.

Posted by Charlotte Schubert at 12:16 PM | Permalink | Comments (0)

Swine flu is entering the mixing bowl. The virus that emerged this spring in Mexico is now reaching the place where it may have its greatest potential to mutate—the tropics. Cases have recently been identified in India, Vietnam and the Philippines.

Flu viruses circulate year-round in tropical regions, where they can mix with each other, mutate and spawn new strains. Two studies published last year outlined this process, showing how seasonal flu strains in the temperate regions originate in tropical regions.

Unfortunately, as Declan Butler at Nature reports, surveillance networks are often weak in tropical countries, so it may be difficult to monitor the evolutionary trajectory of the new H1N1 virus.

Vaccine experts breathed a sigh of relief when the first sequences of the new H1N1 virus revealed relatively little variability among isolates. That makes it easier for manufacturers to produce a vaccine that could work against all forms of the virus. But the virus may surprise us in the fall, popping up as a different sort of beast—or beasts.

There are also fears that the virus will wreak havoc in sub-Saharan Africa, where there are many people living with HIV, weakening their immune system and possibly increasing their vulnerability to swine flu.

Posted by Charlotte Schubert at 02:43 PM | Permalink | Comments (0)

Normally I'm bored to tears reading articles about our broken health care system in the United States and how to fix it. I'd almost rather rememorize the steps of glucose metabolism--the absolutely worst part of being a biology major.

But finally someone has made the subect readable--that expert at medical prose, Atul Gawande. His article in the latest issue of the New Yorker is an insightful read.

He takes us on a tour of McAllen, Texas, the town with the most expensive health care system in the country. Here, it seems, doctors routinely send patients to surgery who might not need it. Doctors have financial relationships, some legal, some apparently not, with hospitals and other institutions that do surgery, imaging and testing. It all has the effect of funneling money into doctors' wallets and ramping up the costs for Medicare, the primary payer in the county.

In contrast, he notes that the famous Mayo Clinic provides much less expensive care. The incentives in this system, and others like it, are set up so that doctors focus more on the patient; they spend more time with them, they consult more with specialists in other fields, and perform fewer unecessary procedures. The result is not only less expense, but radically better patient care.

As the debate on health care ramps up this summer, I'm happy that there are some people out there who devour policy papers on health care like it's candy. For them, this might be old news. For the rest of us, Gawande makes it come alive.

Posted by Charlotte Schubert at 01:39 PM | Permalink | Comments (0)

Hard-hitting head of CDC

Last Friday, President Obama chose a firebrand to head the US Centers for Disease Control.

Thomas Frieden is known for pushing through a ban on smoking in public spaces in New York City, where he has served as health commissioner since 2002. He refused to take that position until the mayor promised to back his plan. After that he took aim at artificial trans fats in restaurants, instituting a ban that inspired other communities to do the same.

He’s likely to put the CDC’s focus back on tobacco, the nation’s number one killer. But he’s also got the creds on infectious disease—having bolstered needle exchange and condom distribution programs in New York, along with supporting a controversial program to increase HIV testing. In the early 1990’s, he ran the city’s tuberculosis program, putting the kibosh on an illness that had taken hold in the city’s vulnerable populations.

Not all of his ideas have been conventional, and some are unpopular. To get an idea of how he gets things done, see this profile by our former news editor, Apoorva Mandavilli.

Posted by Charlotte Schubert at 07:10 AM | Permalink | Comments (0)

In the flurry of closing our May issue last week, one of the authors working with me balked.

“If I’d known you were going to ask me to sign so many forms, I wouldn’t have said yes to commenting! ”

Ok, so we felt like a faceless, inflexible bureaucracy. And, our staff duly explained --in the bureaucratic monotone of an email correspondence–why we need so many %##** forms!

One of those—the conflict of interest form—has become a familiar staple at biomedical journals, conferences, and just about every where else physician-scientists set foot. Except in their own home: Too many research institutions still have weak conflict of interest policies.

The Institute of Medicine has now joined a host of other organizations weighing in on the issue. This week they released their report on financial conflict of interest, outlining a series of recommendations for institutions, including medical colleges.

The report weighs about as much as ‘Molecular Biology of the Cell’—and its contributors seem themselves to have been thoroughly vetted for conflict of interest. Overall, its recommendations, though thorough, are perhaps not surprising. For instance, the report said that, with certain well-vetted exceptions, physicians should not participate in clinical trials in which they have a financial interest in the outcome , and professional societies should not accept direct industry funding for developing clinical guidelines.

The report also recommends that Congress pass legislation—which is being considered--that would require medical device and pharmaceutical companies to disclose publicly all payments they make to physicians. With such a database, medical colleges could make sure researchers—even ones who claim they are next to God—are being straight with them.

All of this sounds good to me. But there’s one recommendation I particularly agree with: get all the conflict of interest scolds—that includes us—on the same boat. Essentially, the report called for more uniformity in policies.

At the press conference announcing the report, committee chair Bernard Lo mused that some software developer (presumably someone ‘detail oriented’) could make filling out the forms, with all their various formats, easier.

Here—fighting sheaves of paper, irritated authors and corrupted pdf files—that’s a reform I could get behind!

Posted by Charlotte Schubert at 03:51 PM | Permalink | Comments (1)

Swine flu continued to make headlines today when the World Health Organization today raised the pandemic threat alert to level 5 (out of 6).

Many news reports have referred to the Spanish Flu, which killed approximately 50 million people worldwide. Starting off as a relatively mild infection in the spring of 1918, the virus proved much more deadly when it returned in the fall. According to a 2008 article, this increase in lethality could have been due to a relatively weak virus mutating to become a stronger one or a respiratory bug circulating in the fall that made patients sicker in the second infection wave (J Infect Dis. 198, 1427–1434; 2008).

It seems that US and British soldiers exposed to the 1918 flu virus in the early stages of the disease were more likely to be protected from or survive the second wave of illness than those not exposed to the first wave. Given this, the authors suggested that “if a mild first [flu] wave is documented, the benefits of cross-protection during future waves should be considered before implementing public health interventions designed to limit exposure.”

What does that mean for us today? No one knows whether this outbreak will stay as is, become milder, or become more deadly. Authorities still do not know the ratio of deaths or serious illness to mild cases, meaning they don’t even know if it is currently a ‘mild’ outbreak. But lessons from the past suggest that this story will stay with us for some time.

Photo by Eneas

Posted by Kirsten Dorans at 04:19 PM | Permalink | Comments (0)

Three new studies published in the April 9, 2009 issue of The New England Journal of Medicine show conclusive proof that adult humans do indeed have appreciable amounts of brown adipose tissue. Why is this important? For at least two reasons: 1) it puts to rest the issue that adult humans have this cell type (more on this below), and 2) if the numbers or the activity of these cells could be increased it could help in the fight against obesity.

So what exactly is brown adipose tissue? Well, when most people think of adipose tissue they think of white fat - the cell type that stores fat for future energy needs of the body (though experts think it is also useful for keeping fats away from other critical organs, like the liver and muscle, and preventing the excess fat from inhibiting their function). But brown fat has another purpose entirely - it burns fats and carbs to release heat, which in turn keeps the body warm. For animals that can shiver, like adult humans, it was believed that brown fat wasn't needed or if it was present it was a vestigial organ that wasn't important for normal physiology. These three studies show that cold temperatures induce the occurrence of this tissue and that it is indeed likely important for normal physiology. More importantly, though, the findings also suggest that because these cells are present they could be targeted to fight obesity, as mentioned above. Indeed, as one of the papers points out, if as little as 0.1% of a person's body weight is converted to brown adipose tissue it could account for ~20% of the adult body's daily energy expenditure.

But there is also an interesting background to these three studies, which all three papers cite and two explain a bit, but it might be interesting to spell out a little further here. The technique the three papers used to identify the brown fat is to give volunteers radiolabeled glucose ([18]F-fluorodeoxyglucose) followed by PET-CT scans. But this technique has been around for awhile. It was originally devised because it was noticed that tumors are quite energy intensive and thus more likely to take up this radiolabel more quickly than normal, healthy cells. Thus it was hoped the technique would allow advanced tumors and their metastases to be visualized. But around 2002-2004 a number of reports started to appear in the radiological literature pointing out that patients tested in this way showed several 'blobs' of staining in the supraclavicular area. Given what we know about the energy expenditure of brown fat, the authors of those earlier studies suggested that adult humans do indeed have appreciable levels of brown fat. But it wasn't until the new studies published this month that this staining was shown conclusively to be cold-inducible and, more importantly, upon biopsy that the cells are indeed brown adipose tissue, as characterized by histology and molecular marker analysis.

Time will only tell now if this cell type in adult humans can indeed be manipulated to keep us trim.

Posted by Randy Levinson at 04:01 PM | Permalink | Comments (0)