Physicians have long recognized that the same disease can behave differently from one patient to another, and that there is no one-size-fits-all treatment.
In cancer, chemotherapy might dramatically shrink one lung tumor but prove ineffective against the same type of tumor in a different patient – even though tissue samples look identical under the microscope. Side effects and appropriate dosage may vary from patient to patient as well.
The goal of personalized medicine is to match a treatment to the unique characteristics of an individual patient: his or her personal and family medical history, age, body size, and other physical characteristics, and medical test results. But fundamentally, it is the DNA blueprint within cells that strongly influences a person’s risks of disease, how illnesses play out, which drugs are likely to be most effective and with the fewest side effects. This is where the newest phase of personalized medicine is heading.
Today, the power of genomics and other DNA tools to uncover molecular patterns in the cells of patients – or in cancer patients, in the cells of their tumors – offers the potential to deliver precision treatment with maximum effect and safety. These molecular patterns reflect differences in the activity of genes and proteins, or abnormal changes – such as mutations – in the DNA code of genes, that increasingly are being used to select the best treatment.
Researchers envision a future in which doctors could routinely prescribe “the right drug in the right dose to the right patient” initially, instead of experimenting with one treatment after another. The results could be less wasted time, expense, and health complications caused by adverse side effects. Genomic information can also help doctors make more accurate prognoses and better estimates of disease risks.
Oncologists have been practicing personalized medicine since before the term was coined. Already this kind of personalized treatment is giving patients a better chance of longer life.
For more than 25 years, treatment of some cancers has been guided by mutations and other DNA flaws in cells that cause tumors to form and spread, such as the so-called “Philadelphia” chromosome abnormality found in most patients with chronic myelogenous leukemia (CML). In the late 1990s, the drug Gleevec was developed to block the harmful activity of the chromosome glitch, becoming one of the first “targeted” or “smart” cancer drugs: It has greatly improved the outlook for patients with CML.
Since then, discoveries at Dana-Farber and in cancer laboratories around the world have been used to devise tests for gene mutations in diseases like blood, lung, breast and colon cancer and malignant melanoma. Patients with these cancers are routinely tested at Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC), and if they are found to have certain mutations, are prescribed precision drugs to block their activity, or may be offered clinical trials of experimental drugs designed to attack those mutations.
For example, patients whose non-small cell lung cancers contain an EGFR mutation may respond well to the drug erlotinib, while those whose tumors have a scrambled ALK gene often do well when given another targeted drug, crizotinib. On the other hand, the presence of a KRAS mutation in colorectal cancer signals that the tumor probably won’t respond to certain targeted drugs for that disease.
With a massive cancer genome research project called Profile, scientists at Dana-Farber and Brigham and Women’s Hospital are building one of the world’s largest databases of genetic abnormalities in cancer, a resource that will make possible a wealth of studies on the genetic roots of the disease. Every patient at DF/BWCC, and now pediatric cancer patients treated at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, is offered the opportunity to participate in the study; to date, nearly 20,000 have consented.
For each participating patient, Profile scientists are analyzing DNA samples of their cancers, using a new “next-generation” sequencing technology that scans cancer-related genes for mutations and other DNA alterations. From the results of these scans, pathologists can determine the particular set of abnormalities that are driving the cancer: a personalized tumor profile. More than 5,000 individualized tumor profiles have been generated by the project in its first two years.
Because these profiles reveal the fundamental molecular causes of a cancer, they may be more important in guiding treatment than standard classification based on where the tumors develop – breast, colon, lung. Personalized treatments guided by the molecular traits of a tumor are at an early stage. To fulfill the promise of this approach, scientists need to amass huge amounts of data linking DNA alterations to tumors’ behavior and how they respond to specific drugs. As one of the largest research efforts to do this, Profile is a major contributor to the future of cancer care.