Personalized Oncology? 2009
The latest buzzword in cancer is "personalized oncology." The phrase originated mid-decade, especially in relation to nanotechnology. John Niederhuber, MD, director of the National Cancer Institute, endorsed personalized oncology in his Cancer Bulletin editorial of August 19, 2008, where he wrote about the dawn of an era of "personalized cancer medicine," with "specific, targeted therapeutic solutions."
"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....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" (Niederhuber 2008).
I also believe in personalized oncology, but I have serious doubts about the commitment of the cancer leadership to this concept. Beyond the rather limited testing of breast cancer patients for standard receptors, I can think of few situations in which treatment is actually being personalized in a significant way for the typical patient. Treatment still seems to be chosen based on predetermined protocols for particular stages of the disease, usually according to anatomically-defined tumors rather than individual characteristics. These protocols are chosen based on empirical evidence derived from previous clinical trials. A particular drug or combination of drugs is favored because on average it performs somewhat better than another combination. The key word here is "average." There is nothing individual about this approach.
As far as I can tell, when the vast majority of oncologists suggest treatment protocols, they are relying on the standardized recommendations of the National Comprehensive Cancer Network (NCCN), or some other authority, rather than individualizing the choice of drugs based on the characteristics of the individual in their office.
All of this talk about personalized oncology, however, has raised expectations among patients. Blogging at Medscape.com, oncologist and pathologist Cary A. Presant, MD explains the public relations dilemma that doctors now face:
"The first implication [of personalizing oncology, ed.] is that the way in which we communicate with patients has to change. Because patients are seeing personalized cancer care as a recurring emphasized theme in newspapers and television, it is important for each oncologist to assure patients that their treatment plans are optimized for personalized therapy."
In other words, oncologists need to reassure their patients that they are indeed getting "the best and most up-to-date care...." Dr. Presant does not address the question of whether this in fact is true.
Dr. Presant also states that surgeons must be informed that fresh tumor tissue removed during biopsies or operations needs to be preserved for microarray DNA testing, "or for cellular essays (for example chemotherapy sensitivity or drug induced apoptosis which can personalize care for patients with leukemia and solid tumors)."
In other words, personalized cancer care often involves the use of cell culture drug resistance testing. It is wonderful to see this recommended in print from such an eminent source. But here's the problem. Chemosensitivity testing based on apoptosis (programmed cell death) has been around for quite a while. Since the 1980s, it has been denigrated and resisted by the cancer establishment, and has been championed by unconventional practitioners. The battle has been a bitter one. How then will the cancer establishment suddenly reconcile its new emphasis on personalized oncology with its previous opposition to such tests? This will require NCI, ASCO and the other large cancer organizations to do an about face on an issue which has long divided them from integrative oncologists.
Here is how Larry Weisenthal, MD, one of the pioneers of chemosensitivity testing, summarized the situation earlier this year:
"In the late 1980s, the NCI...effectively closed down research into fresh human tumor cell culture methods for testing and optimizing chemotherapy. The proof of this is the complete lack of NIH-funded studies relating to this topic appearing in PubMed for the last 15 years. Instead, we have put all of our clinical trials resources into trying to identify the best treatment for the average patient - in a disease notorious for heterogeneity....All of a sudden, there is a belated recognition that 'personalized' therapy is [a] worthy goal - yet 100% of the effort is going into static profiling of molecular markers, as opposed to dynamic, functional profiling of tumor response ex vivo. It's crazy/nuts, and, down the road, tomorrow's translational researchers will shake their heads and say 'What on earth were they thinking?'"
In my opinion, the issue of chemosensitivity testing is a big rock in the road for this new approach. Personalized oncology sounds great, but is unlikely to be implemented until some influential individuals within the establishment stick their necks out and point out that NCI has been on the wrong side of this debate for years. Until then, personalized oncology is likely to remain just an attractive slogan rather than a real paradigm shift.
--Ralph W. Moss, Ph.D.
Niederhuber, John. The Dawn of Personalized Oncology. Cancer Bulletin (National Cancer Institute), August 19, 2008. Available at:
Presant, Gary A. Personalized Oncology Care: A New Paradigm For The Oncologist And Patient, Medscape Hematology/Oncology, Sep 4, 2009.
Accessed at: http://tinyurl.com/ylqnkqv
Schrag, Garewal, Burstein, Samson, Von Hoff, and Somerfield. American Society of Clinical Oncology Technology Assessment: Chemotherapy Sensitivity and Resistance Assays. JCO. 2004;22:3631-3638.
Larry Weisenthal's excellent blog: