War against cancer has more than one target

[Guest guest]

Sorry that didn’t carry over well. Here is the full article:

Washington Post

By Brown

Tuesday, April 27, 2010

Declaring a " war on cancer, " President Nixon signed the National Cancer Act on Dec. 23, 1971, in a White House room full of happy scientists and proud politicians.

The quaintness of the idea of a " war on cancer " says a lot, in fact, about how much we've learned in the past 39 years.

It's true that in one sense cancer is still a single disease, defined then and now as a state of uncontrolled growth in cells. What's different in 2010 is that scientists understand at the molecular level dozens of different ways that cancerous cells achieve the state of uncontrolled growth (with more being discovered every year). They know that the differences are sufficiently great that there will never be a singular " cure for cancer " -- but that the differences may point the way toward lots of very good treatments.

The deconstruction of " cancer " into its hundreds of varieties -- each of which can be labeled by its own DNA mutation, chromosomal translocation, gene amplification or other defect -- may be the biggest achievement of the war on cancer.

It's not just that leukemia, osteosarcoma and breast cancer are different in the genetic defects underlying them. Each of those has subtypes with a somewhat different menu of defects that may affect how they respond to treatment. Even within the subtypes, some tumors are especially dependent on one defect or another for their bad behavior, even if the defect is widely shared.

Misleading appearances

Harold J. Burstein, a physician and researcher at the Dana-Farber Cancer Institute in Boston, likes to draw an analogy between cancer and pneumonia.

A lot of cancers look fairly similar under the microscope, just as many types of pneumonia look similar on X-rays. But appearances are misleading, because the invisible differences are more important in the long run. You really don't understand pneumonia (and probably can't treat it very well) until you understand how different the disease caused by influenza virus is from the one caused by the tuberculosis bacterium or the histoplasmosis fungus.

" The kind of 'speciation' that microbiologists figured out was behind pneumonia a hundred years ago is what is now happening in cancer medicine, " Burstein said.

Most experts think it takes more than one derangement in a cell's genes to " transform " it into a cancer cell. What's indisputable is that cancers tend to acquire more errors over time, gaining behavior -- such as the ability to spread to distant organs (metastasize) or resist the effects of drugs -- not present in the first small cluster of tumor cells. The piling-up of errors is also why a tumor isn't a pure-bred collection of cells but a mixture, with many cells having their own private defects in addition to the ones they share with their brethren.

Targeting these errors with drugs that locate and block a defective gene or its protein product is the newest strategy of cancer treatment.

This " targeted biological therapy " may be less toxic than conventional chemotherapy, which seeks to kill all rapidly dividing cells and inevitably takes down a lot of normal ones in the process. Like chemotherapy, it can extend survival, sometimes by years. But targeted therapy doesn't appear able to cure, which chemotherapy occasionally does. It simply leaves too many untargeted cells alive at the end of the day.

Whether that will change when physicians have dozens of new biologic drugs at their disposal is a big unanswered question in oncology.

The first step

If cancer is a disease of accumulated errors, the first error is the most important. It sets a new trajectory for the cell and is present in all the descendants. Most cancer researchers believe that if one were able to undo that first step, or block its effects, long-lasting benefit would result even if cure didn't.

That's what appears to be happening with imatinib (Gleevec), a drug used to treat chronic myelogenous leukemia. It targets the defective form of a gene called ABL that all patients with the disease seem to have and that, once acquired, initiates this kind of leukemia.

Gleevec causes remission of the cancer in 95 percent of patients; nearly that percentage are still alive five years later.

" It is the best anti-cancer drug ever developed, " said Carlo M. Croce, a physician and cancer geneticist at Ohio State University Medical Center.

The trouble is that for most cancers -- and especially those of " solid organs, " such as breast, lung, colon and pancreas -- the initiating defect isn't known. For most of those in which it is known, including some blood cancers other than chronic myelogenous leukemia, there aren't yet drugs that target the defect.

But cancer research isn't a story of never-ending complexity, as much as it appears to be.

Thanks to whole-genome scanning of many tumors, scientists think they've identified nearly all the big actors in cancer: the genes commonly mutated across many types of cancer. That, in turn, has revealed the existence of perhaps a dozen " core pathways " in cell physiology and behavior that are damaged in cancer.

" Out of all this complexity there may be some common themes, " said Victor Velculescu, a physician and cancer researcher at s Hopkins University who has done much of this work. " There are common pathways shared between many tumors, even though the individual genes affected in a pathway are different. "

The search is underway for drugs that target pathways rather than damaged genes. The goal is to block the chain reaction of events leading to uncontrolled cell growth somewhere downstream from the one (or more) genes that are causing the problem. That way one " targeted therapy " could target numerous cancers.

It will be a long war.

On 4/27/10 10:51 AM, " fskelton@... " <fskelton@...> wrote:

<http://www.washingtonpost.com?referrer=emailarticle> E-mail <http://altfarm.mediaplex.com/ad/ck/14302-93014-2151-3?mpt=430474>

This page was sent to you by: fskelton@...

War against c! ancer has more than one target <http://www.washingtonpost.com/wp-dyn/content/article/2010/04/26/AR2010042603361.html?referrer=emailarticle>

By Brown

Declaring a " war on cancer, " President Nixon signed the National Cancer Act on Dec. 23, 1971, in a White House room full of happy scientists and proud politicians.

<http://ad.doubleclick.net/jump/wpni.email/emailafriend;ad=bb;kw=emailafriend;ord=1272379898998?>

Do you love D.C.? Get the insider's guide to where to stay, what to do and where to eat. Go to www.washingtonpost.com/gog <http://www.washingtonpost.com/gog/index.html?r!eferrer=emailarticle> for your guide to D.C. now.

© 2010 The Washington Post Company | Privacy Policy <http://www.washingtonpost.com/wp-srv/interact/longterm/talk/members.htm?referrer=emailarticle>