HonCode

Go Back   HER2 Support Group Forums > Articles of Interest
Register Gallery FAQ Members List Calendar Search Today's Posts Mark Forums Read

Reply
 
Thread Tools Display Modes
Old 12-29-2005, 03:42 AM   #1
sarah
Senior Member
 
Join Date: Sep 2005
Location: france
Posts: 1,648
Fighting Cancer's Achilles Heel

From the International Herald Tribune, Tuesday:
http://www.iht.com/bin/print_ipub.ph...ews/cancer.php


Finding cancer's Achilles' heels
By Gina Kolata The New York Times
TUESDAY, DECEMBER 27, 2005

Jay Weinstein found out that he had chronic myelogenous leukemia in 1996, two weeks before his marriage.

He was 36 and he thought his health was great. But by 1999, his disease was nearing its final, fatal phase. He might have just weeks to live.

Then Weinstein, a New Yorker, managed to become one of the last patients to enroll in a preliminary study at the Oregon Health and Science University in Portland, Oregon, testing an experimental drug.

Weinstein is alive today and still taking the drug, now on the market as Gleevec. Its maker, Novartis, supplies it to him free because he participated in the clinical trial.

Dr. Brian Druker, an investigator at the university's Cancer Institute who led the Gleevec study, sees Weinstein as a pioneer in a new frontier of science. His treatment was based not on blasting cancer cells with harsh chemotherapy or radiation but instead on using a sort of molecular razor to cut them out.

That, Druker and others say, is the first fruit of a new understanding of cancer as a genetic disease.

A person may inherit a predisposition to cancer, but it can take decades - even a lifetime - to accumulate the additional mutations needed to establish a tumor. That is why, scientists say, cancer usually strikes older people and requires an element of bad luck.

"You have to get mutations in the wrong place at the wrong time," Druker says.

Other genetic diseases may involve one or two genetic changes. In cancer, scores of genes are mutated or duplicated and huge chunks of genetic material are rearranged.

With cancer cells, said Dr. William Hahn, an assistant professor of medicine at Harvard Medical School, "it looks like someone has thrown a bomb in the nucleus."

At first, as scientists grew to appreciate the complexity of cancer genetics, they despaired.

"If there are 100 genetic abnormalities, that's 100 things you need to fix to cure cancer," said Dr. Todd Golub, the director of the Cancer Program at the Broad Institute of Harvard and MIT in Cambridge, Massachusetts, and an oncologist at the Dana-Farber Cancer Institute in Boston.

Making matters more complicated, scientists discovered that the genetic changes in one patient's tumor were different from those in another patient with the same type of cancer.


But to their own amazement, scientists are finding that untangling the genetics of cancer is not impossible. In fact, they say, what looked like an impenetrable shield protecting cancer cells turns out to be flimsy. And those seemingly impervious cancer cells, Golub said, "are very much poised to die."

The story of genes and cancer, like most in science, involves many discoveries over many years. But in a sense, it has its roots in the 1980s, with a bold decision by Dr. Bert Vogelstein of Johns Hopkins University to piece together the molecular pathways that lead to cancer.

It was a time when the problem looked utterly complicated.

But Vogelstein had an idea: What if he started with colon cancer, which had some unusual features that made it more approachable?

Colon cancer progresses through recognizable phases. It changes from a tiny polyp, or adenoma - a benign overgrowth of cells on the wall of the colon - to a larger polyp, a precancerous growth that, Vogelstein said, looks "mean," and then to a cancer that pushes through the wall of the colon. The final stage is metastasis, when the cancer travels through the body.

"This series of changes is thought to occur in most cancers, but there aren't many cancers where you can get specimens that represent all these stages," Vogelstein said.

With colon cancer, pathologists could get tissue by removing polyps and adenomas in colonoscopies and taking cancerous tumors in surgery.

Colon cancer was even more appealing for such a study because there are families with strong inherited predispositions to develop the disease, indicating that they have cancer genes that may be discovered.

So Vogelstein and his colleagues set out to search for genes "any way we could," he said. Other labs found genes, too, and by the mid-1990s, scientists had a rough outline of what was going on.

Although there were scores of mutations and widespread gene deletions and rearrangements, it turned out that the crucial changes that turned a colon cell cancerous involved just five pathways. There were dozens of ways of disabling those pathways, but they were merely multiple means to the same end.

People with inherited predispositions to colon cancer started out with a gene mutation that put their cells on one of those pathways. A few more random mutations and the cells could become cancerous.

But scientists were stymied. Where should they go from there? How did what happens in colon cancer apply to other cancers? If they had to repeat the colon cancer story every time, discovering genetic alterations in each case, it would take decades to make any progress.

The turning point came only recently, with the advent of new technology. Using microarrays, or gene chips - small slivers of glass or nylon that can be coated with all known human genes - scientists can now discover every gene that is active in a cancer cell and learn what portions of the genes are amplified or deleted.

With another method, called RNA interference, investigators can turn off any gene and see what happens to a cell. And new methods of DNA sequencing make it feasible to start asking what changes have taken place in what gene.

The National Cancer Institute and the National Human Genome Research Institute recently announced a three-year pilot project to map genetic aberrations in cancer cells.

The project, Druker said, is "the first step to identifying all the Achilles' heels in cancers."

Solving the problem of cancer will not be trivial, Golub said. But, he added, "For the first time, we have the tools needed to attack the problem."

Robert Weinberg, a biology professor at the Massachusetts Institute of Technology, said, "We're close to being able to put our arms around the whole cancer problem."

"We've completed the list of all cancer cells needed to create a malignancy," Weinberg said. "And I wouldn't have said that five years ago."

Golub said that it takes "a couple of dozen mutations to cause a cancer, all of which are required for the maintenance and survival of the cancer cell."

Gleevec, researchers say, was the first test of this idea. The drug knocks out a gene product, abl kinase, that is overly abundant in chronic myelogenous leukemia. The first clinical trial, which began seven years ago, seemed like a long shot.

But the clinical trials of Gleevec were a spectacular success. Patients' cancer cells were beaten back to such an extent that the old tests to look for them in bone marrow were too insensitive, Sawyers said.

Gleevec is not perfect. It is expensive, costing about $25,000 a year. It is not a cure: Some cancer cells remain lurking, quiescent and ready to spring if the drug is stopped, so patients must take it every day for the rest of their lives. And some patients are now developing resistance to Gleevec.

Still, Sawyers says, "Seven years later, most of our patients are still doing well." Without Gleevec, he added, most would be dead.

And some cancer therapies may have to be taken for a lifetime, turning cancer into a chronic disease.

"Seeing cancer become more like what has happened with AIDS would not be shocking," Golub says. "Does that mean cure? Not necessarily. We may see patients treated until they die of something else."

That is what Weinstein hopes will happen with him. The cancer is still there: New, exquisitely sensitive tests still find a few cells lurking in his bone marrow. And Gleevec has caused side effects. Weinstein says his fingers and toes sometimes freeze for a few seconds, and sometimes he gets diarrhea.

But, he said, "Certain things you put out of your mind because life is so good."
sarah is offline   Reply With Quote
Old 12-29-2005, 01:20 PM   #2
Rich
Guest
 
Posts: n/a
"New, exquisitely sensitive tests still find a few cells lurking in his bone marrow."

What are these tests? Useful for her2+ BC?
  Reply With Quote
Old 12-31-2005, 04:58 AM   #3
Unregistered
Guest
 
Posts: n/a
Interesting particularly;

Each cancer is "unique". (Treatment and hope implications - dilution of certainties - implied argument for treatment with close monitoring of impact "biofeedback" Gina's phrase)

Limited pathways are key. (If implicated somthing as simple as fat intake balance could make a huge difference)

Caused by gentic change. (An evolutionary disease and above a base level of genetic disposition a response to environmental / dietary factors growth of many tunours to 1cm takes many years)

Thought provoking post, thank you ,

RB
  Reply With Quote
Reply

Thread Tools
Display Modes

Posting Rules
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts

BB code is On
Smilies are On
[IMG] code is On
HTML code is On

Forum Jump


All times are GMT -7. The time now is 10:59 PM.


Powered by vBulletin® Version 3.8.7
Copyright ©2000 - 2024, vBulletin Solutions, Inc.
Copyright HER2 Support Group 2007 - 2021
free webpage hit counter