I wish u knew… Genomics & Cancer

Tim Hampshire

Here are a few things I learned while talking to Dr. Anil Rustgi:

  1. Scientists meticulously keep track of family history in the mice on which they conduct genetic tests.
  2. Cells are not special; they can be grown on plastic.
  3. There are three things that influence cancer: genetics, environment, and “something intrinsic in the host.” The third one is the wild card. It’s not easy to create experiments that account for cosmic whimsy.
  4. Most tumors are heterogeneous, meaning they are like mixed bags of genes gone wrong. That means each tumor is different. That’s why it’s tough to keep track of which genes or absences of genes cause cancer.
  5. The Cancer Genome Atlas, run by the NIH, is probably the coolest website ever (besides OncoLink, of course.)

Dr. Rustgi discusses genomics and cancer and translating laboratory research into clinical practice.

It is hard to come away from a conversation with Dr. Rustgi with anything but notes and observations. He’s eager to talk science, showing the particular elegance of his work life in facts and figures. He’s right to get excited about his work, which is in the genomics of cancer—how it develops, where it develops, and how to stave it off at the genetic source. Mostly, he uses mice.

Dr. Rustgi and his colleagues are stunningly careful about how the mice are used. They have the full capability to recapitulate tumor growth in mice, study how inherited malignancies emerge in “families” of mice, and introduce factors that influence cancer growth in humans. High fat diets, alcohol consumption, cigarette smoke, UV radiation—all of it is used, according to the thick book of regulations published by the FDA, to study how cancer emerges in mice, and thus how it emerges in humans.

Yes, it really does happen the same way in both species. I asked him.

The purpose of the experiments is not to just study the origin of cancers, but also to create an impact in public health.

Gene therapy, and the tests that precede it, are preventive measures. If we all know who’s likely to get cancer, what cancer’s we’re likely to get, and other similar information, and we know it with some certainty because it’s encoded in our DNA, we should be able to prevent ourselves from getting it. This is both a noble goal and a problem that faces the field. “I think as a community or society we tend to gravitate towards therapy…It’s intuitively more attractive. But it’s more challenging and more expensive. I would argue that prevention is actually equally laudatory,” Dr. Rustgi told me. So why do we gravitate toward therapy when prevention is really what will solve the problem? Unfortunately, that’s probably something we’ll always do. You can build levies, but the UN won’t be there until the flood hits. That’s just the way it is; we have to do something, right? People have cancer right now. We have to treat it.

Dr. Rustgi also sees a logical fallacy in the way the public approaches prevention. He said, “With prevention, the positive outcome is the absence of something.” True: this is also the case for therapies. But with therapies, there is the presence of the enemy. Solve the problem, and you’re being heroic. Make it impossible, and you’re being paranoid. That’s the way we think. There has to be an ill for there to be a cure.

Dr. Rustgi thinks on a larger scale. In a way, the genomic war on cancer is like the international War on Terror. The threat could come from anywhere. The vast majority of people, like the vast majority of cells, will live out their days without even considering an attack on the public. The vast majority of cells who consider attacks on the public, like the vast majority of people who consider attacks on the public, do not carry them out. But it’s that tiny little sliver of the pie that blows the whole thing up. So the problem, like Dr. Rustgi said, is how to make sure something very unlikely does not happen. That’s hard.

But it’s getting easier. There are tests now that can offer sequencing options to anyone with enough money. I know that sounds out of touch. Hear me out: the tests are getting cheaper and cheaper. It’s like what happened with the computer. Tests that used to take hundreds of thousands of dollars in investments from large organizations are now floating around $1,000. They will get more accessible. Dr. Rustgi assures me that this is the direction in which we are moving.

The final problem is a logistical one. I asked Dr. Rustgi if, in an ideal world, we would all carry around our genetic portfolios, perhaps on a little USB around our necks.

“In an ideal world?” he asked. “Absolutely.”

It was his surest answer he gave me in the whole interview.

But there was still a caveat: where do we store that information? Once we have it, how do we keep it on file? That’s a huge technological investment.

Luckily, the NIH has that website I mentioned in the above list. Check it out. The Cancer Genome Atlas is a project that takes dozens of types of cancer and lists the genetic information about tumor samples from those cancers. It does it in a creative and easily accessible data matrix that can be downloaded on any computer. “I’m very excited about the project,” said Dr. Rustgi. Indeed, the Genome Atlas is a fantastic indicator of the direction of the field, and we might need to do a little more of whatever it’s doing if we’re ever going to get to the absence of something.

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