The Register’s online science page will periodically feature guest essays, columns and book excerpts, most of them written by Orange County college and university professors. We begin this feature with a column by Daniele Struppa, (bio) chancellor of Chapman University in Orange. Struppa, who also is a mathematician, wrote his piece exclusively for The Register.

The Promise of Personalized Medicine

A few days ago I visited a friend who is in his last days of his life. He was diagnosed with an advanced stage esophageal cancer a couple of years ago: he fought valiantly, but the battle is now over, and so is his life.

Because of our friendship, and because of my personal scientific interest in cancer, I followed his battle more closely than I would have otherwise done. When, after a year, it was apparent that the standard treatments were not able to help him, he became one of the many patients to attempt what now goes under the name of theranostics (the discipline that develops a tailored approach to the disease of a specific individual) and which is one of the great promises in our battle against cancer (already several cancer research institutes are developing facilities and research programs directed to personalized medicine; recent investments in this direction have been made by the Center for Molecular Oncologic Pathology at the Dana-Farber Cancer Institute, and the Center for Targeted Therapy at the Anderson Cancer Center at the University of Texas).

Cancer remains an extremely difficult disease to treat, and every day, in the United States, about 1,500 people die of the disease. Interestingly enough, the percentage of Americans who die of cancer is the same now, as it was in 1971, when President Nixon declared the ‘war on cancer,‘ and most of the improvements in cancer mortality are due to changes in lifestyle and in the progress in early diagnostics.

Cancer is difficult to treat because it is difficult to predict which therapy will work on a specific patient. The reason for this difficulty is that two patients with the same cancer may respond very differently to the same therapy. And this is because even though two patients may have the ’same cancer’, in fact the cancers may be quite different at a deep level which is not easy to detect through the standards tests such as a biopsy.

To understand what cancer is, we need to look at the building blocks of our body, our cells. Different organs have different cells, but they all share fundamental behaviors: they absorb energy and transform that energy so to be able to survive, grow, and reproduce. The way in which they transform energy is through a very complex network of proteins. We can think of a cell as a large (very large) network of power plants (the proteins) connected with each other. At any given time, one or more of the plants is active, and energy flows from one plant to another. If one of the plants shuts down, or if any other difficulty arises, the system is in generally sufficiently resilient, and the energy flow can be redirected so that the general functioning of the plant is ensured. This explains why we don’t get cancer every day. Most alterations in the network don’t need to be repaired.

The cause of cancer, in this metaphor, is found in the fact that the network of interactions between the power plants (proteins) in a cell become severely impaired. Usually this means that the cell becomes immortal and reproduces rapidly. It is this immortality, and the rapid growth, that produce the cancerous growth. In order for us to defeat cancer, we need to know in which way the network is impaired, and two cancers which may appear to be the same, may in fact be the result of two very different impairments. If this is the case, the cancers will respond to two very different cures.

Thus, when a patient needs therapy, the best way to provide such therapy is to fully understand the interactions between the proteins in his cancerous cells. Only by understanding such interactions we can hope to be able to develop a targeted therapy.

Theranostics attempts to do exactly this. Instead of offering a standard treatment to all the patients with the same type of cancer, the goal of theranostics is to analyze the specific protein network in the cancer of the patient, and on that basis develop or identify the drug that most likely can repair the impairment in the network. Such analysis is not otherwise possible with clinical methods, and offers a much deeper understanding of the cancer at hand.

The analysis of the specific network impairments have already offered unexpected results. For example, Gleevec is a targeted drug which was developed in 2004 and proved to be extremely effective to treat a certain kind of leukemia (chronic myeloid leukemia). However, because of its action on specific parts of the protein networks, it has now been found that Gleevec is also extremely successful in treating some kinds of solid Gastrointestinal cancers, which apparently have no connection whatsoever with leukemia.

When my friend realized he had no chance with standard therapy, he underwent one more biopsy of his liver methastases to see whether it was possible to conduct a proteomic analysis of his cancerous cells that would suggest a different therapy.

As it turned out, the targeted drug that was eventually prescribed did not reach its goal. My friend passed away recently, but the promise of this new approach is very much alive, and is likely to change radically the way we think of cancer in the next fifteen to twenty years.

This entry was posted on Friday, April 18th, 2008 at 9:00 am and is filed under Chapman Univ. science news, Guest columns. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed.