The science of large numbers

From Shanghai, China, to the American South, modern-day gumshoes are hot on the trail of some of the worst miscreants afflicting the human race. By surveying thousands of participants enrolled in “cohort studies,” researchers are uncovering important clues to cancer and other diseases.

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Hitting the bull’s-eye

They’re not “magic bullets,” but targeted therapies have dramatically improved outcomes for many cancer patients. These drugs are not without side effects, however, and some of them cost $10,000 a month. Vanderbilt researchers give an update on the search for better treatments.  read article

In the beginning

It could be nature’s cruelest joke—the genes and proteins that help sculpt the fertilized egg into a complex multicellular organism are also responsible for the birth of many cancers. Understanding the fundamentals of developmental biology could lead to new treatments for patients.  read article

Piercing the body with precision

The scalpel is giving way to the scan—at least in some cases of cancer.
New imaging technologies are raising hopes that doctors soon will be able to locate tumors with pinpoint accuracy, and track their hour-by-hour response to treatment—without the need for surgery.
Coupled with recent advances in genetics and molecular biology, imaging is speeding the discovery and evaluation of safer, more effective treatments that can stop tumors in their tracks.
“In the past 10 years we’ve made tremendous strides in improving imaging of cancer,” says Dennis E. Hallahan, M.D., chairman of Radiation Oncology at Vanderbilt University Medical Center. “In the near future we will be using functional imaging to image pre-cancer.”  read article

A new view of cancer

Tumors are not islands unto themselves. They can “hijack” normal cellular processes, including inflammation, to hide from the body’s immune system. They can “re-educate” inflammatory cells to release factors that promote tumor growth and spread. The ability to peer into this malevolent microenvironment is giving researchers new ideas for stopping tumors in their tracks.  read article

High-tech surveillance

Proteomics, the science of proteins, has raised hopes that doctors one day will be able to detect early cancer from tell-tale patterns of proteins in a single drop of blood. What will it take to bring these methods into the clinic?  read article

Eric Lander: The great amplifier

A driving force behind the sequencing of the human genome, Eric Lander is now tackling the “cancer genome.” More than that, this mathematical wunderkind wants to empower the next generation of scientists with new tools and information so they can “change the world.”  read article

Symphony of knowledge

The crab on the cover of this issue of Lens magazine represents all that is old and new about cancer, the nation’s second leading cause of death after heart disease.

Old, because cancer goes back to the dinosaurs; evidence of malignancies has been found in fossils dating back 80 million years.  read article

An enduring legacy

One of the exciting potentials of cohort studies is that the collected data can be used by other researchers to address questions that are important to their areas of interest—for years to come.  read article

What’s Caterpillar got to do with it?

Cohort studies are important research investments, says Harvard epidemiologist Walter Willett, M.D., MPH, Dr.P.H.

“They’re necessarily long-term investments, too, and as such, they are particularly vulnerable to cutbacks in research funding,” he says.  read article

One arrow’s not enough

Think of targeted therapies as poison arrows piercing Achilles’ heel.

There’s validity to the idea that the new generation of drugs “take advantage of our improved knowledge of the biology of cancer to exploit weaknesses in its defenses,” says David Johnson, M.D., a lung cancer specialist at Vanderbilt-Ingram Cancer Center.  read article

The next targeted therapies

We’re hitting a plateau and facing a gap of several years before the next targeted therapies emerge from pre-clinical and early stage clinical trials, says Mace Rothenberg, M.D., director of the Phase I Drug Development Program at Vanderbilt-Ingram.  read article

A quiver of cancer fighters

Drug Approved in For treatment of By targeting Avastin 2004 colorectal cancer VEGF*   2006 lung cancer VEGF Erbitux 2004 colorectal cancer EGFR   2006 head and neck cancer EGFR Gleevec 2001 CML bcr-abl    2002 GIST* c-kit*, PDGFR* Herceptin 1998 breast cancer HER-2  Iressa 2003 lung cancer EGFR Nexavar 2005 kidney cancer Raf kinase* Sprycel 2006 CML  bcr-abl  Sutent 2006 kidney cancer, GIST VEGF receptor, PDGFR, c-kit Tarceva 2004 lung cancer EGFR

 * VEGF—vascular endothelial growth factor; GIST—gastrointestinal stromal tumor; c-kit, Raf kinase—proteins linked to tumor growth; PDGFR—platelet-derived growth factor receptor.  read article

Turning genes on to turn cancer off

Cancer can result not only when certain genes are “turned on,” but when others are “turned off” by the attachment of chemical “tags” to the DNA. This tag-driven control of gene expression—called epigenetics—provides a new avenue for stopping tumor growth.  read article

How to crack the cancer code

In 2003, 13 years and $2.6 billion after it started, the Human Genome Project completed the sequence of nearly all of the 2.9 billion letters of genetic code that make up the human being.

Now researchers are tackling what may be an even more ambitious challenge – developing an “atlas” that describes the genetic characteristics of the more than 200 different types of cancer.  read article

Bonanza or boondoggle?

Can the sequence of the human genome be used to find genes that cause cancer?

A study published in 2006 in the journal Science suggests that it can.

Researchers at Johns Hopkins University in Baltimore, Md., compared the protein-coding regions of genes in 22 samples of breast and colorectal cancer to the corresponding “normal” sequences. After eliminating errors and normal variations, the study yielded 189 candidate cancer genes, most of which had never been seen in tumors before.  read article

Embryo’s cellular ‘dance’ may choreograph cancer, too

One of the classic examples of aberrant activation of a developmental pathway in cancer is the APC gene, a component of the Wnt signaling pathway. People with mutations in this gene, named for adenomatous polyposis coli, a pre-cancerous polyp found in the colon, have a high risk of developing colorectal cancer at a young age.  read article

Pathway to glioma?

The Hedgehog (Hh) signaling pathway plays a critical role in embryonic development and has been linked to a number of different types of cancer.

Researchers at Vanderbilt University Medical Center are now examining its role in one of the most fatal types of brain tumors—gliomas.  read article

A problem of social injustice

Harold Freeman, M.D., former president of the American Cancer Society, and Jane Weeks, M.D., chief of Population Sciences at the Dana-Farber Cancer Institute, discuss what needs to be done to reduce the disproportionate impact of cancer on racial and ethnic groups, the poor and the elderly.  read article

Edge of the world

In 2006, Lens magazine asked four leading scientists about the ethics of genomics research. Should we direct our own evolution? Are there places we shouldn’t go?

Kay Davies, D.Phil., associate head, Department of Physiology, Anatomy and Genetics at Oxford University, and honorary director of the Medical Research Council’s Functional Genetics Unit:

Cloning is one of those places we shouldn’t go.  read article

Lwala diaries – a postscript

The previous issue of Lens chronicled the efforts of Vanderbilt medical student Milton Ochieng’ to construct the first health clinic in his village in Kenya. Abbie Foust, who spent her summer vacation surveying his village’s health needs, describes her life-changing experiences.  read article

A Closer Look at Drugs

Just as imaging technologies are guiding and, in some cases, replacing the scalpel, they are revolutionizing the evaluation of new cancer drugs.

Traditionally, a drug’s effectiveness has been determined by its impact on patient survival, or by measuring the diameter of a tumor on a series of X-rays or CT scans taken over the course of several weeks.  read article