Defeat Osteosarcoma

It’s been 40 years since President Richard Nixon signed the National Cancer Act. NCI has spent $100 billion on understanding cancer biology since then – the equivalent of $10, or two designer cups of coffee, per U.S. resident per year – and billions more have been spent developing new drugs and treatments to work against those biological processes.

Still, cancer kills more than 566,000 people worldwide each year, the equivalent of three 747s crashing every single day.

Today, serious people argue that our whole strategy in solving the cancer problem might be wrong, that too much effort has gone into understanding cancer and not enough into simply applying what we already know. Cancer scientists like myself have even heard claims that we’re ignoring solutions to the cancer problem-that we’re sitting on “the cure for cancer.”

The truth isn’t pretty: Cancer death rates are declining, yet improvement in cancer mortality has lagged behind other killers like cardiovascular disease. Only about 5 percent of new cancer drugs that are tested in people get approved for clinical use, compared with about 20 percent of cardiovascular drugs. This number doesn’t count the number of drugs that fail before they are tested in people.

Although we’ve made much progress, we don’t even fully understand how the most fundamental decisions in cell biology occur, such as how cells decide to die or grow.

Here’s one reason why we need more – much more – understanding of cancer biology. We are taking on the most powerful force in biology: Darwinian natural selection.

A tumor is a population of many types of cells that are all trying to grow and survive. When we treat cancer, we are trying to kill the tumor cells (or stop their growth) by applying strong selective (or evolutionary) pressure. And, cancer cells evolve to avoid selection we applied-the “fittest” cancer cells survive.

Cells that grow back after treatment probably found a way to avoid that treatment. We see this in the clinic: When tumors come back, they usually don’t respond to the drugs that worked before.

This problem of Darwinian selection pressure doesn’t really apply to other major diseases in which cells die because they are damaged-think heart or neurodegenerative disease.

The best hope we have of making a big impact on the number of people who survive cancer is to understand even more about how the biology works. For example, by understanding how cell growth and survival are controlled, we might predict how tumor cells will undergo natural selection to avoid a drug’s effects and be able to design a strategy to stop cells from beating the treatment.

We have some examples of this already. We know that tumors that use a growth pathway called EGFR can be stopped for a while using an EGFR inhibitor drug. Eventually, the cells find another pathway to use to grow. We’ve figured out that these EGFR-positive tumors use a bypass mechanism driven by a cell receptor called Met.

By understanding how the cells use Met to grow when their preferred EGFR growth pathway is blocked, we’ve learned we can combine EGFR and Met inhibitors to kill more cancer cells than using either agent alone.

However, for most cancer drugs, we don’t know what pathways cancer cells might activate to get around a drug-induced roadblock. Until we do, we will probably continue to throw away potentially useful treatments. Indeed, I suspect that some of those 95 percent of failed cancer drugs would have been useful if only we knew more about how they worked.

We need more research into cancer biology, because without really understanding what is going on, our efforts to apply that research will be doomed to failure. Understanding cancer biology isn’t just the best way forward; it is the only way forward, if we really want to solve the cancer problem.

Dr. Andrew Thorburn is interim director of the University of Colorado Cancer Center and professor and vice chair of Pharmacology at the University of Colorado School of Medicine. He holds the Grohne Chair in Basic Cancer Research. Learn more about cancer research in Colorado at www.uccc.info. EDITOR’S NOTE: This is an online-only column and has not been edited.