Genome and Metabolic Scans the new anti-Cancer Weapon

New cancer treatments are one of the most precipitous of all drugs to develop. But a renewed focus on the DNA mutations that make each cancer unique is about to expand our ability to find new treatments.

Cancer biomarkers may be detected using Mass Spectrmoetry

Traditionally, cancer drugs have been developed by identifying compounds, more recently antibodies, that have a highly toxic effect on cancer cells and animal models in the lab. They are then tested on small, then larger groups of patients to prove their efficacy. But this model is yielding less and less success. In the last 30 years, for example, there has been no real improvement in the drugs able to treat metastatic melanoma from which about 1000 Australians die every year.

The reason is that scientists have been slow to figure out ways to truly capitalize on our molecular knowledge of cancers. Our approach to disease is very linear – X mutation leads to Y disease – despite us knowing that most diseases are polygenetic in origin.We tend to work on particular molecular pathways in isolation. For example, individuals labs will often use one animal model for their own research.

In this article, the founders of Sage, a biomedical networking company, explain how our approach has to begin to use our knowledge of full molecular networks. They say that much of Merck’s metabolism pipeline was developed using such molecular knowledge.Another great example is the AstraZeneca/Biowisdom Safety Intelligence Program (SIP), described as the “largest forever-expanding collection of known chemical effects occurring in different tissues, drug effects on clinical biomarkers of tissue injury, and drug molecular mechanisms.” Currently, SIP contains almost 100,000 individual facts, or “assertions,” related to the liver’s response to more than 5,500 different compounds in over 20 species.

Fundamentally, this new style of research relies on powerful new approaches to sequencing and decoding genomes – something that DNA arrays initially promised, but never really delivered. I’ve previously written on this topic, but every month new astounding results come out of cutting edge labs that herald a new era in molecular science and particularly cancer treatment.

Helicos Biosciences, a company founded in 2004 to commercialize single DNA sequencing technology has just become the fourth next-gen sequencing platform to complete a genome. At the same time, a second leukemia genome has been fully sequenced leading to discoveries of previously unknown mutations and new potential drug targets.

The next step is to capitalize on these discoveries by testing the association between these markers and the various drugs on offer. As an example, these researchers at MIT have found that when both p53 and ATM (common tumor markers) are abnormal, tumors are highly susceptible to DNA-damaging chemotherapy. Tumors in which ATM is mutated but p53 is not, are highly resistant to chemotherapy. Tumors in which p53 is mutated but ATM is not seem to be less responsive to chemotherapy.

This is a solution that is applicable immediately. “You could use this today,” the author says. “You do immunohistochemistry for the tumor, for p53 and ATM, and based on [the results] you can choose anthrocyclines [if appropriate], or taxol as an alternative based on this data.”

Drug companies are beginning to use bio-markers more and more in their studies, but I would contend still not enough. If you do a medical literature search of recent cancer clinical trials, how many trials report collecting bio-markers such as p53 and ATM?

In a closely related field – metabolic profiling–an analysis of chemical reactions in the body- there has been a positive recent advancement. Metabolic profiling may help optimize drug use in patients.

Today, most doctors rely on broad measures like weight, sex and age to determine which drug and dose is most likely to be effective. It’s a notoriously hit-or-miss approach that commonly requires follow-up doctor visits and changes in drugs and dosing. Now are groups of UK scientists have determined that the chemicals created during the process of metabolism and then excreted in the urine could be a more effective tool for personalizing therapies.

To test their theory, scientists at Imperial College London and Pfizer took a urine test of 99 men who were given paracetamol, a common painkiller. What they found was that ascertaining the level of a compound in the urine–para-cresol sulphate–gave the scientists a clear picture of how the men would metabolize the drug. Higher levels of the compound, which is produced in the gut, indicated that men would metabolize the drug less effectively. They theorized that higher levels of the compound indicated that their bodies were depleted of sulphur, which many drugs rely on to work safely. Sulphur helps to detoxify the body. Engineering the bacteria in the gut could fine tune how a body metabolizes a drug.

The advantage of this pre-dose metabolite profiling is that it related to both genetic and environmental factors influencing drug treatment outcomes. Again, this is another step that will soon put an end to centuries old hit-and-miss medicine.

Friends: the secret to longer life

Many of my medical colleagues agree that the more you learn about medicine, the less hope you place in its ability to solve people’s real health concerns. At the same time, we are rediscovering the power of  non-medical, merely natural everyday things. Science is resurrecting ordinary life from its perhaps recently neglected past.

Friendship is a good thing, no one doubts it. But do we seek friendship out as we seek wealth or medical treatment? Yes and no, I believe. We all yearn after friendships, but we often see them fail. We all know people with few friends, and perhaps see others failure to make the effort to maintain friendships that are usually rather fragile (as fragile as the human will perhaps).

The one exception would be in the realm of mental health where the role of friendship is emphasised by therapists seeking to reconnect their patients to a world they are distancing from.

Now we should be pleased to hear that not only can friendships help fight depression, but they can help treat other illnesses, speed recovery, slow aging and prolong life.

From the New York Times:

Researchers are only now starting to pay attention to the importance of friendship and social networks in overall health. A10-year Australian study found that older people with a large circle of friends were 22 percent less likely to die during the study period than those with fewer friends. A large 2007 study showed an increase of nearly 60 percent in the risk forobesity among people whose friends gained weight. And last year, Harvard researchers reported that strong social ties could promote brain health as we age.

“In general, the role of friendship in our lives isn’t terribly well appreciated,” said Rebecca G. Adams, a professor of sociology at theUniversity of North Carolina, Greensboro. “There is just scads of stuff on families and marriage, but very little on friendship. It baffles me. Friendship has a bigger impact on our psychological well-being than family relationships.”

In a new book, “The Girls From Ames: A Story of Women and a 40-Year Friendship” (Gotham), Jeffrey Zaslow tells the story of 11 childhood friends who scattered from Iowa to eight different states. Despite the distance, their friendships endured through college and marriage, divorce and other crises, including the death of one of the women in her 20s.

Using scrapbooks, photo albums and the women’s own memories, Mr. Zaslow chronicles how their close friendships have shaped their lives and continue to sustain them. The role of friendship in their health and well-being is evident in almost every chapter.

Two of the friends have recently learned they have breast cancer. Kelly Zwagerman, now a high school teacher who lives in Northfield, Minn., said that when she got her diagnosis in September 2007, her doctor told her to surround herself with loved ones. Instead, she reached out to her childhood friends, even though they lived far away.

“The first people I told were the women from Ames,” she said in an interview. “I e-mailed them. I immediately had e-mails and phone calls and messages of support. It was instant that the love poured in from all of them.”

When she complained that her treatment led to painful sores in her throat, an Ames girl sent a smoothie maker and recipes. Another, who had lost a daughter to leukemia, sent Ms. Zwagerman a hand-knitted hat, knowing her head would be cold without hair; still another sent pajamas made of special fabric to help cope with night sweats.

Ms. Zwagerman said she was often more comfortable discussing her illness with her girlfriends than with her doctor. “We go so far back that these women will talk about anything,” she said.

Ms. Zwagerman says her friends from Ames have been an essential factor in her treatment and recovery, and research bears her out. In 2006, a study of nearly 3,000 nurses with breast cancer found that women without close friends were four times as likely to die from the disease as women with 10 or more friends. And notably, proximity and the amount of contact with a friend wasn’t associated with survival. Just having friends was protective.

Bella DePaulo, a visiting psychology professor at the University of California, Santa Barbara, whose work focuses on single people and friendships, notes that in many studies, friendship has an even greater effect on health than a spouse or family member. In the study of nurses with breast cancer, having a spouse wasn’t associated with survival.

While many friendship studies focus on the intense relationships of women, some research shows that men can benefit, too. In a six-year study of 736 middle-age Swedish men, attachment to a single person didn’t appear to affect the risk of heart attack and fatalcoronary heart disease, but having friendships did. Only smoking was as important a risk factor as lack of social support.

Exactly why friendship has such a big effect isn’t entirely clear. While friends can run errands and pick up medicine for a sick person, the benefits go well beyond physical assistance; indeed, proximity does not seem to be a factor.

It may be that people with strong social ties also have better access to health services and care. Beyond that, however, friendship clearly has a profound psychological effect. People with strong friendships are less likely than others to get colds, perhaps because they have lower stress levels.

Last year, researchers studied 34 students at the University of Virginia, taking them to the base of a steep hill and fitting them with a weighted backpack. They were then asked to estimate the steepness of the hill. Some participants stood next to friends during the exercise, while others were alone.

The students who stood with friends gave lower estimates of the steepness of the hill. And the longer the friends had known each other, the less steep the hill appeared.

“People with stronger friendship networks feel like there is someone they can turn to,” said Karen A. Roberto, director of the center for gerontology at Virginia Tech. “Friendship is an undervalued resource. The consistent message of these studies is that friends make your life better.”

Proteomic breakthrough – the future of blood tests.

Cell Biosciences, Inc., a provider of nanoproteomic analysis systems to life science researchers, today announced the publication of a landmark study by a research team from Stanford University School of Medicine.

The publication, titled “Nano-fluidic proteomic assay for serial analysis of oncoprotein activation in clinical samples”, details new methods for detecting small modifications in cancer-related proteins.

Their method allows the use of as little as 4 nanolitres of sample, and is able to measure signalling changes in 25 cells. This would allow repeated smapling to determine cancer regression.

Assuming the technology is transferable to other proteomic applications, we might consider a future nanolitre-scale serum tests for a range of markers!!