Institute for Prostate Cancer Research

IPCR Director's Corner Newsletter October 2013

Director's Corner

October 2013

IN THIS ISSUE  

Prostate Cancer Precision Medicine

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.

Yours,

Paul Lange signature

Paul H. Lange, M.D., FACS
Professor, Department of Urology, UW Medicine
Director, Institute for Prostate Cancer Research


Prostate Cancer Precision Medicine

Peter Nelson, M.D.
Member, Division of Human Biology, FHCRC

Professor, Department of Medicine, University of Washington

Dr. Lange asked me to share some groundbreaking developments by researchers within the IPCR ACT-SMART research initiative that pertains to Cancer Genomics. We embarked on this ambitious endeavor in response to the evolving field of so-called “Precision Medicine” and its exciting relevance to cancer treatment.

What is Precision Medicine?

Precision medicine uses a patient’s individual genetic and genomic information to more accurately design treatments that are targeted and effective. By building on the scientific and technological advances made possible by the completion of the Human Genome Project in 2003, researchers have found ways to rapidly and comprehensively identify important inherited variation in a patient’s genes – that may predispose an individual to cancer, and mutations, acquired during the development of a tumor – that are responsible for driving cancer growth. Importantly, specific mutations also signal which tumors are likely to respond to certain therapies and thus allow individualized ‘precision’ treatments designed to maximize the likelihood of success and minimize futile therapy and avoid side-effects.

Genomics: a discipline in genetics that analyzes the structure and function of genomes, the complete set of DNA within a cell of an organism http://en.wikipedia.org/wiki/Genomics

Genetics (from Ancient Greek genetikos, “genitive” and that from genesis, “origin”), a discipline of biology, is the science of genes, heredity and variation in living organisms. http://en.wikipedia.org/wiki/Genetics

What is New?

The genome consists of linear sequences of four DNA nucleotides, or bases. By analogy, these four bases, A,T,G,C, can be considered the ‘letters’ of the genetic code much as 26 letters comprise our alphabet. The specific order and length of segments of these bases are what defines individual genes, much as the specific order and length of letters in our alphabet define words. In humans, every cell contains a copy of the entire genome—more than 3 billion DNA bases. The process of sequencing is determining the order of DNA bases in a genome and determining whether any letters vary between individuals or are missing or out of order, called a mutation. Most variants are harmless, but some inherited variants can put people at higher risk of developing cancer. Further, some mutations are particularly susceptible to certain drugs leading to ‘targeted therapy’. While DNA sequencing has been around for decades, the process was slow and expensive. A recent major technological advance, termed Next Generation Sequencing (NGS) provide a rapid and accurate approach for determining the order of bases for the entire genome.   Using NGS, a person’s constitutional genome (what you inherited from your parents) and tumor genome (the mutations that occurred to cause the cancer cell to develop and grow) can be determined and potentially used to guide important medical decisions concerning cancer screening, preventing cancer and other diseases, and guiding treatment strategies for cancers that are detected.

The Future of Prostate Cancer Treatment

Precision medicine has clear implications to revolutionize cancer treatment. Genetic driven precision medicine has advanced our understanding of cancer mutations and has created the platform to work towards cancer treatment that can:

  • Personalize risk assessments in patients and families to drive preventative measures
  • Translate to clinical trials to identify new reliable treatment techniques for a given gene mutation
  • Identify and catalog prostate gene mutations to design effective treatment for a broad spectrum of unique prostate cancer subtypes
  • Provide safer, more cost effective care by tailoring cancer treatment to the specific needs of each patient and avoiding side-effects of unnecessary therapy.

While cancer genomics serves as a key component of ‘Precision Medicine’, the full-realization of personalized medicine will include other rich sources of data that builds on information from family history, populations, the environment, exposures (e.g. to diet, infectious organisms) and importantly, is adaptable to change over time. Collectively, this ‘Information Commons’ concept has been likened to a ‘Geographic Information System’ (GIS) exemplified by Google Maps. In this map structure, key information concerning car traffic patterns, housing prices, nearby-restaurants, population density, weather, and many other data types are anchored around a geographical location. You likely use these powerful applications everyday with your smart phone. In the context of health, the information is centered around a given individual patient, and higher layers of information can be readily accessed to address, interpret and predict complex health problems and improve disease outcomes.

As you can imagine, precision medicine techniques are changing the way we think about cancer treatment. These techniques provide the tools to tackle prostate cancer with greater reliability using therapies that are tailored for the individual’s specific needs. This is the reason IPCR researchers developed the ACT-SMART research initiative briefly explained by Dr. Lange.  This is a large complex effort that cannot be covered in one issue.  Here we will describe what will be the first of many increasingly sophisticated cancer genetic tests that we expect to apply to the real time management of prostate cancer patients. In subsequent Director’s corner issues we will describe more of our activities and plans in the ACT-SMART initiative. Now it is important to state again that such an ambitious enterprise could not have been conceived and implemented without the generous support and encouragement of so many individuals. 

The UW-OncoPlex™

UW researchers, led by Dr. Colin Pritchard and colleagues, developed a unique diagnostic test; it focuses on 200 key cancer-associated gene mutations. The UW-OncoPlex™ technology is the first nationally to detect treatable genetic changes and then use this information to recommend a specific type of treatment based on this information. The panel has undergone rigorous assessments of accuracy and reproducibility and is certified by CAP and CLIA, two key hospital laboratory accreditation mechanisms that ensure adherence to quality control standards. This test panel is currently being used for a variety of cancers, but researchers with the IPCR have developed 8 precision genome targets focused on prostate cancer. Our team is currently setting up the prostate cancer test panel for clinical use. With the support of ACT-SMART initiative funding, over the next year, we expect to use this prostate cancer panel to determine precision targets for advanced prostate cancer patients. This work hopes to integrate UW-OncoPlex™ testing for advanced prostate cancer patients into routine clinical care.

If you would like to find out more information about Oncoplex cancer genomics guiding precision medicine, please see:

http://www.seattlecca.org/diseases/oncoplex-overview.cfm

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