For decades we’ve known that cancer is caused by variation and mutations in genes; those a person is born with and those that become mutated during one’s life. We’ve also known for some time that while cancers can be categorized into broad types such as breast cancer, lung cancer, prostate cancer and so forth, at the gene level the cancers within each type are still significantly different between cancer victims. Finally, more recently, we have learned that drugs specifically developed to attack the abnormal gene(s) present in some cancer types can kill tumor cells and put its victims into remission often without debilitating side effects. This is co-called “targeted therapy” to be distinguished from classical “chemotherapy” which non-specifically poison susceptible cancer cells but also normal cells and thus is usually associated with significant side effects. Two dramatic examples of targeted therapy are Herceptin in breast cancer and Gleevac in chronic myelogenous leukemia (CML) that specifically neutralizes the abnormal gene product of the Her2/neu gene and the BCR-abl gene in breast and CML cancers respectively. But not all breast and CML cancers have these defective genes and it is clear that other genetic changes drive these cancers. Thus the dream of many cancer researchers is to sequence all the genes in the cancer, find which ones are abnormal and critical to abnormal growth, and then find (or develop) specific drugs that target these abnormal genes as they develop and/or gain prominence in the cancer’s growth. Until recently this dream was totally impractical if not impossible. That’s because it used to take years to totally sequence and compute a person's normal or tumor genome at a cost in the hundreds of thousands of dollars.
Now that dream is a possible. Using very sophisticated sequencing and computing techniques whole genomes can be determined within 2 months for costs that are declining rapidly and currently are in the range of 10 thousand dollars and dropping quickly. Thus research teams who possess advanced sequencing techniques and patient resources such as exist within the Institute for Prostate Cancer Research (IPCR) are rushing to make this revolutionary opportunity available for patient treatment.
Thus several years ago the IPCR launched an ambitious program which we called ACT-SMART. In a word we intend to sequence the whole genome of patients and their prostate cancers, determine the most important abnormal genes of the cancer, identify agents that target these abnormal genes and so treat the patient. This very ambitious endeavor requires a major commitment of talent and resources.
In this issue I have asked Dr. Peter Nelson to begin an explanation of this milestone enterprise. He is a medical oncologist who treats advanced prostate cancer patients, directs a large gene research laboratory, and now is our leader of the IPCR research team. A complete discussion of this effort will take several Director Corner issues but I am confident that when completed you will be convinced of its promise, persuaded that the IPCR is in a very unique position to exploit this opportunity, and excited about the prospects that this activity will move us closer to much better control if not cure not only of prostate cancer but also of other cancers as well.
Paul H. Lange, M.D., FACS
Professor, Department of Urology, UW Medicine
Director, Institute for Prostate Cancer Research