Figuring out what makes cancer tick

The Cancer Genome Atlas Pilot Project

The NCI and NHGRI have launched a project to figure out what causes cancer at the DNA level. This Cancer Genome Atlas Project has been touted in the media as a big deal. And it is.

If it works, it could lead to more effective cancer medicines with fewer side effects. To understand how this project could accomplish this, we need to go over what cancer is, how cancer drugs work and how The Cancer Genome Atlas Project will work.

What is cancer

Back in the 1970's, Richard Nixon started a war on cancer. Researchers quickly found out that cancer wasn't a single disease and so there wouldn't be a single cure.

Scientists now know that cancer is actually a large collection of at least 200 different diseases. What they all have in common is that they start out as cells that have gone wild.

Cancer starts out as a cell, just sitting there, minding its own business. Suddenly, something happens to the cell's DNA.

Maybe the sun has caused a mutation in a gene in a skin cell. Or, the cell has just divided and it made a mistake when it copied its DNA. Or something in cigarette smoke has mutated the DNA of a lung cell.

Whatever caused the DNA change, this mutation in the gene has unleashed the cell's ability to grow and divide. A cell is usually under tight control and is only allowed to grow and divide a certain amount in certain places.

Now, because of the DNA mutation, it is free to grow, make copies of itself and even spread out a bit. This is the definition of cancer.

There isn't just one mutation that causes cancer, though. Lots and lots of DNA changes can lead to a cell growing uncontrollably (or refusing to die). And once a DNA mutation has happened, more tend to happen so that you end up with lots of DNA changes.

It's all of these changes that The Cancer Genome Atlas Project wants to find. By finding these changes, the hope is that scientists can find better treatments for cancers.

Treating cancer

Right now, most cancer treatments are based on the fact that cancers grow very quickly and most of the rest of our cells don't. In fact, most of our cells grow hardly at all once we're adults.

So what cancer drugs do is kill any growing cells. Different cancers respond better to different general killers, but by and large most of these different medicines just clobber growing cells.

Of course you kill the other growing cells in your body too. Which is why these treatments cause hair to fall out, nausea, anemia, etc. The hair follicles, lining of the digestive tract and red blood cells are all bludgeoned by the treatment as well.

And the treatment doesn't even work with some slow growing cancers like prostate cancer. So doctors would like to have more subtle medicines that really target just the cancer cell.

These drugs would work by targeting specific broken genes found in the cancer. Remember, cancer happens when our DNA is changed or mutated.

Cancers are usually classified by what tissue they started out as—breast, prostate, lung, etc. But within these classes there are different subtypes. These subtypes arise because cells become cancerous due to different DNA changes.

Change X leads to a breast cancer that can be treated one way, change Y leads to a breast cancer that can be treated another way. What the Cancer Genome Atlas Project hopes to do is to find different ways to treat all of these subtypes.

We already have an example of a drug like this for breast cancer—Herceptin. Herceptin targets cells in which a specific gene, her2, has been turned on. Herceptin kills only the cells that make her2, the cancer cells. This means Herceptin eliminates the cancer more effectively with fewer side effects.

But not all breast cancers make her2. What this means is that Herceptin doesn't work on the other cancers, only the cancers that make her2.

What the Cancer Genome Atlas is designed to do is to find more genes like her2. The hope is that drugs can then be developed that target these genes so that only the cancers and not the other cells will be eliminated. This should lead to fewer side effects as well.

More Information

Most cancer drugs kill any growing cell

The Cancer Genome Atlas Project

Scientists have already found her2 and a few other genes involved in cancer. And lots of scientists are working on this problem as we speak. So what is so special about this project?

The difference is the scale of the project and the new tools being used to tackle the problem. We can compare it to the Human Genome project.

Before figuring out all of the A's, C's, G's and T's of people's DNA, scientists were sequencing bits of the human genome. We were finding out about our DNA in small fits and starts and everything took a long time to do.

Once all of the DNA was sequenced, everything went faster. If you found something interesting, you could quickly get the DNA involved. Before it would take months or years—now it could be done with a few keystrokes on the computer and a simple experiment.

You also could now see everything all at once. This allowed scientists to see connections and relationships where none could be seen before.

The situation before the Human Genome project was sort of like trying to describe what an elephant looked like when you can only see the trunk. You could learn a lot about the trunk and take some educated guesses about what an elephant looks like, but you probably wouldn't get everything right.

The Human Genome project let us see the whole elephant. And The Cancer Genome Atlas Project will let us do the same for cancer.

We'll now be able to see the whole of cancer and see what genes are involved. If common genes are involved in two types of cancer, then maybe we'll be able to treat them with the same medicine.

Knowing all (or at least lots more of) the genes involved in cancer will also get us to medicines faster. How?

Once we have a gene, we can test it to see if it is involved in cancer. If it is, we can see if blocking it will stop or kill the cancer. If blocking the gene kills the cancer, scientists can then design or screen for drugs that can block the gene.

Now, this is still a long process and it won't happen overnight. But the project will eliminate one of the most time consuming steps in the process—finding culprit genes.

What was announced on 12/13/2005 is money for a pilot project. All of this sounds great but may not work for a number of technical reasons.

So the NCI and NHGRI are putting up 100 million dollars to test this idea on two or three different cancers. If all goes well, the remaining 3 billion or so dollars will be released.

Let's hope all goes well. Half of all U.S. men and a third of its women will develop cancer in their lifetime. This project holds the promise of finishing what President Nixon started in the 1970's—finding a cure for cancer.

Cancers are caused by DNA mutations