Although not well-known to those of us in the general public, there is excitement in the air at many cancer centers and research laboratories. A promising method of treating tumors – based not on the type of cancer but on the genetic mutations that cause it – is on the verge of entering into clinical trials. Much work in the laboratory yet needs to be completed and there are plenty of “no guarantees” uttered. Nonetheless, this program appears loaded with hope for some eventual breakthrough. It is doubtful that a cancer patient who has heard of this approach will not stay tuned for further developments.
1) The Historic Approach:
Historically, cancer has been treated by the type of cancer. For example, colon cancer patients received treatments that were forged by research into colon cancer; ovarian cancer patients were treated with therapies based on ovarian cancer research. Sometimes an overlap was discovered, allowing one treatment of one cancer to benefit a patient with a different type of cancer. Even then, each cancer in each person was different. As the National Institute of Health stated in a September 2013 press release on the Cancer Genome Atlas (TCGA): “Cancer is not a single entity, but rather, it is more than 100 complex and distinct diseases, with most individual cancer types demanding unique treatment strategies.”
2) The Genetic Approach:
In recent years, the focus of cancer research has continued on individual types of cancer, but at the same time it has expanded into looking at cancer based on the genetic mutations causing or contributing to the tumors – that is, there has been a cross-tumor analysis taking place. Since the mid-2000s, TCGA, a joint venture supported by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), has been analyzing genetic aspects of tumors. In a recent paper discussing the project, genome.gov stated that TCGA’s initial research papers showed that “a limited number of genetic alterations are responsible for most cancer sub-types, and that mutations most often occur in certain regions in the genome.”
As the NIH explained in the above cited press release, “TCGA has been generating and analyzing data according to the organ in the body from which a tumor first arose” and “has published eight papers examining genomic changes in tumor types.” The findings, however, have provided new insight into the cause of many cancer cells. Specifically, “researchers have uncovered shared molecular patterns among cancers, including similar genomic changes occurring across tumor types.” NIH September 2013 Press Release. Because of these findings, in 2012 TCGA started what is known as the Pan Cancer Project, through which it has been undertaking a formal cross-tumor analysis. NIH September 2013 Press Release; see MD Anderson September 2013 Press Release.
3) Clinical Trials Are Starting:
One of the next steps involves testing the various hypotheses in clinical trials. As nature.com stated in a detailed October 2013 article about the Pan-Cancer Project, “But the true power will come from a detailed analysis across tumor types—with links to high-quality clinical outcomes and eventual experimental validation and clinical trials to test the hypotheses that emerge.” The GenomeWeb Daily News, quoting a research scientist from Memorial Sloan-Kettering, put it this way in a September 26, 2013 release: “In future clinical trials, we envision that patients with a certain type of endometrial cancer, for example, may be enrolled in the same trial as patients with a subtype of colorectal cancer,” Memorial Sloan-Kettering Cancer Center researcher Chris Sander, co-senior author on the oncogenic signature study, said in a statement, “and that patient selection for clinical trials can be guided by cancer genomics profiling in the clinic.” As GenomeWeb added: “This work is intended to help in the design of such trials . . .and the development of more personalized cancer therapies.”
An article about the Pan-Cancer Project that appeared most recently in the January 16 2014 edition of genome.gov, stated that clinical trials already have started at Memorial Sloan-Kettering and other large cancer centers. As the article explained: “Enrollment in early stage clinical trials is less based on the kidney, lung, colon or other organ site that is affected by cancer, and more on the specific genomic abnormalities seen in the tumor.
. . . [O]ne new approach is the “basket” trial. Rather than treating subtypes of disease only by site of origin, such trials test the effectiveness of a drug on a specific molecular abnormality seen in many different cancers. In a trial, patients with different types of cancer can be grouped into similar or separate baskets.”
We are still in the very early stages. An April 1, 2013 article in The Scientist, entitled “Cancer Clinical Trials Of Tomorrow,” discusses the possible manner in which clinical trials will change with this “precision” approach. The author there predicts that “it is inevitable that there will be a rise in the number of [clinical] trials that incorporate molecular tumor testing prior to treatment, with treatment selection informed by the molecular features of each individual’s cancer. Such personalized trials have the potential to yield better outcomes by increasing the probability of response.”
Stay tuned. This is truly “personalized” medicine. Hope is in the air.