NCI Cancer Bulletin: A Trusted Source for Cancer Research News
NCI Cancer Bulletin: A Trusted Source for Cancer Research News
August 19, 2008 • Volume 5 / Number 17 E-Mail This Document  |  Download PDF  |  Bulletin Archive/Search  |  Subscribe

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Director's Update

The Dawn of Personalized Oncology

Wherever I go, someone invariably asks, "Have we really made any progress against cancer?" My answer is, We definitely have - we have made tremendous progress.

I go on to explain how much more we know today than we did just a decade or two ago. We know that the tumor has a very significant and critical microenvironment in which it grows; that the normal-appearing cells of this microenvironment are genetically reprogrammed to support the growing tumor in the critical steps of invasion and metastasis. We know much more about mutations, changes in gene copy number, translocations, the re-expression of genes involved in embryogenesis, and the epigenetic suppression of other genes - and how these changes lead to the growth and spread of cancer.

This new knowledge is being determined and catalogued at a stunning rate, led by our research efforts in functional biology and by our work in genomics and transcriptional regulation. In addition, whole-genome scans that define regions associated with cancer risk are being identified, fine mapped, and sequenced. The Cancer Genome Atlas (TCGA) project is actively sequencing actual patient tumors and finding new gene alterations associated with a specific cancer's development.

Our newly acquired understanding of cancer is leading to specific, targeted therapeutic solutions and the dawn of an age of highly personalized cancer medicine. The future is upon us, and we are now designing precise therapies to home in on specific targets that result from genomic and functional changes, not only in the tumor cell but also in the tumor microenvironment. We are learning that the complexity of altered cellular communications will require the development of multi-agent treatment solutions, in contrast with single drugs. As a result, the future will require innovative strategies and partnerships - between academia, the public sector, and industry - to change the process of determining efficacy and safety, thereby speeding the progress from laboratory to patients. This is not an insurmountable challenge, but clearly is one that will require NCI's involvement and leadership at every step of the new paradigms.

As you will read in this special issue of the NCI Cancer Bulletin, the National Cancer Institute and its partners are taking steps to enhance the process of drug development, from target identification to high-throughput screening; to chemical characterization and structural design optimization at the molecular target interaction; to testing in genetically engineered mice; to the design of mechanisms for monitoring in vivo activity. At the end of the process is translation into man.

The challenge now is to make sound prioritization decisions about which targets to pursue, and then to move them into a synchronized, efficient platform for development.

To support the critical first steps, a high-throughput screening resource to identify small molecules will complement NCI's Chemical Biology Consortium, a network of institutions that have formally agreed to collaborate in the early phases of the drug discovery process. This will be an integrated research consortium at the interface of chemical biology and molecular oncology - an iterative program in cancer drug discovery.

As potential drugs - small molecules, large molecules, and biologics - emerge, researchers will need to develop new ways to assess their efficacy and establish the proper dosages, given that targeted, selective agents may have an optimal dose much lower than the maximum dose a patient can tolerate. Likewise, we need to develop an improved clinical trials system, to better accommodate targeted therapies and accurately assess genomic changes in patients. The challenge in translation is optimally matching the tumor and therapeutic recipe. Proving the importance of these issues, they were front and center at a recent meeting sponsored by the National Cancer Policy Forum of the Institute of Medicine. Solving them is among NCI's top priorities.

So, have we really made any progress against cancer? Consider, if you will, that at several major cancer centers, researchers are currently developing the next phase of personalized care for lung cancer. After a diagnosis, in this new protocol, patients will have a tumor sample extensively analyzed for alterations in six or seven genes known to be critical in the disease. Patients will then be matched with targeted agents, based on the genetic defining of their tumor. As we move forward, this will be the pattern of treatment for all malignancies. Furthermore, the genetic characterization of patients, in a process termed pharmacogenomics, will greatly assist in determining correct dosages and avoiding unsuspected toxicity due to faulty metabolic pathways.

Indeed, we must take steps now to ensure that in the years ahead, targeted therapies are available for all types of cancer. NCI has the opportunity - the obligation, in fact - to connect and coordinate all components of America's cancer enterprise, to make sure this is an opportunity firmly grasped.

Dr. John E. Niederhuber
Director, National Cancer Institute