What exactly is precision medicine (factsheet)?
"Most medical treatments have been designed for the “average patient.” As a result of this “one-size-fits-all-approach,” treatments can be very successful for some patients but not for others. This is changing with the emergence of precision medicine, an innovative approach to disease prevention and treatment that takes into account individual differences in people’s genes, environments, and lifestyles."
In other words, the goal is to tailor diagnostics and treatments to the individual patient rather than to a mythical "average" patient. People differ from one another in terms of their genetics, environment, and personal physiology. Dr. Francis Collins, head of NIH, mentioned one classic example of precision medicine which is that blood transfusions are based on your particular blood type (A, B, AB or O).
The early focus of the initiative will be on cancer. Cancer is the second leading cause of death in America (only behind heart disease), and is notable and for its deadliness and the randomness with which it chooses its victims including those who are young. We have made significant progress in our War on Cancer over the past 40 years, but the battle is far from won.
In particular, scientists and doctors have learned a lot about mutations to genes that influence the progression of cancer. On the one hand, there are oncogenes that promote cancer progression when they become activated by mutation or chromosomal rearrangements. On the other hand, there are tumor suppressor genes that normally block cancer, but when these genes are inactivated by mutation, then the inhibition is removed. Each different type of cancer (e.g. lung, colorectal, skin, etc.) possesses a different set of causal mutations, and even within a particular type of cancer, the mutations may vary from individual to individual. This mutational diversity has implications for both diagnosis and treatment.
Diagnostics is one area in which precision medicine can make an immediate impact. I have previously blogged about the actress Angelina Jolie who had a family history of breast cancer. When her DNA was sequenced, it was found that she carried a mutation in the BRCA1 gene which is a tumor suppressor gene. The mutation knocked out the functionality of the gene resulting in a greater probability of cancer. Indeed the lifetime risk of breast cancer in patients possessing this type of BRCA1 mutation is 60% compared to 12% for the general female population (a five-fold increase in risk).
Treatment is the other area in which precision medicine will be directed, and one example was described in The New York Times. The article outlines a new program in which the tumors from patients are sequenced to identify cancer-causing mutations. Then the patient would be treated with drugs that are most effective against cancer possessing those particular mutations, thus matching treatment with the individual patient's cancer genetics. This new program is being run by the National Cancer Institute (NCI) and is appropriately called Match:
"The rarity of the mutations, in fact, is one reason for the new national effort, supported by the National Cancer Institute. Its study, called Match, is essentially a basket of basket studies. Doctors around the country will be sending tumor samples from at least 3,000 patients to central labs that will examine them for mutations. Those with any of a dozen or so mutations in their tumors can enroll in studies of drugs that target their tumor’s mutation."
There are several novel aspects to the Match program. First, cancer is not being defined by the tissue type (e.g. liver versus lung) but by the mutations. Second, there are no control groups in these studies (i.e. everyone receives some type of treatment). Third, a large number of different drugs (and drug combinations) will be tried. The overall hope is to find special matches in which specific drugs work particularly well against cancers with specific mutations.
One may expect this program will be particularly effective for rare cancers which currently lack good treatments i.e. pharmaceutical companies tend not to develop drugs for rare diseases because lack of profitability. Indeed, the New York Times article described such a case. A 78 year-old woman possessed a rare white blood cell cancer that just happened to carry the same mutation found in many melanomas (skin cancer). Numerous drugs have been developed to target melanoma and that particular mutation in the BRAF oncogene. When one of these drugs was given to the woman it had a profound effect and cured her. This is the promise of Precision Medicine.
On the other hand, this approach is expected to be less effective against deadly common cancers like ovarian and pancreatic cancer which have been studied extensively and for which numerous therapeutics exist but are only partially effective (i.e. extending life but not curing the patient). Fortuitous "matches" such as that described in the previous paragraph are much less likely to occur. The New York Times article at the end mentions a woman with stomach cancer who was in the Match Program but did not respond to her treatment and died. There are simply some cancers possessing certain types of mutations which have proved refractory to all current treatments.
In the future, we will develop better treatments against these intractable cancers. One key advance will be cataloguing all cancer-causing mutations both individually and in combination (e.g. some mutations tend to appear together). Then we can systematically test panels of drugs (both individually and in combination with one another) against cancers carrying different sets of mutations and identify the mutation-drug matches that work the best. The hope is that we will then be able to perform more of the "miracle cures" described for the woman with the white blood cell cancer.
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