Make your appointment or second opinion with Dana-Farber today to meet with an onsite specialist.

Adult Patients:877-442-3324

Pediatric Patients:888-733-4662

Make Appointment OnlineInternational Patients

Online second opinions

Can’t get to Boston? Explore our Online Second Opinion service to get expert advice from Dana-Farber oncologists.

Request a second opinion

Contact & Directions

Email Dana-Farber

Main Number617-632-3000

Toll-Free Number866-408-DFCI (3324)

Maps & DirectionsContact InformationSend us a Question or Comment

How to Help

Discover the ways to give and how to get involved to support Dana-Farber.

Learn More
Give now

  • Paths of Progress Fall/Winter 2011

    Tailor Made

    How science is designing cancer treatments to fit the genetic makeup of individual patients
    By Richard Saltus

    Some headache sufferers get relief from Tylenol (acetaminophen); others swear by Advil (ibuprofen), Aleve (naproxen), or plain old aspirin – unless the latter drugs make their stomach hurt or bleed.

    You may need to try one painkiller after another to find the one that works best with the fewest side effects – and end up tossing the others in the trash.

    Such inconsistent responses to drugs, encountered throughout health care, drive the growing "personalized medicine" movement. It's an approach that uses new genetic tools to select treatments according to DNA patterns in the cells of individual patients or groups of patients.

    The aim is to streamline treatment, improve outcomes, save time and money, and avoid predictable – potentially fatal – side effects.

    "The right dose of the right drug, for the right patient, at the right time" is the mantra of personalized medicine, whose advocates say it could bring about a revolution affecting much of health care. In personalized cancer care, drugs would be matched to the genetic makeup of the tumor itself.

    This long-term goal underlies the new cancer research program launched by Dana-Farber and Brigham and Women's Hospital (BWH), which together are establishing a research database of tumor genotypes obtained from consenting patients.

    Eventually, this information should lead to more-specific treatments that attack the particular genetic flaws in an individual's tumor, while causing fewer side effects than many current drugs do.

    Although it's taken flight in the past 5 to 10 years, personalized medicine is based on an insight more than a century old.

    "I believe that no two individuals are alike chemically any more than they are structurally," wrote British physician Archibault Garrod in 1898, after studying patients with inborn metabolic diseases. Only much later would scientists learn that these differences are determined by genes, the DNA instructions in cells that form the operating manual for our bodies.

    Patient Groups Illutrations.gifPersonalized medicine recognizes that individual patients may react in very different ways to the same treatment given for the same problem. The goal is to tailor therapies based on a patient's DNA profile. 

    Although 99 percent of DNA is identical in all humans, the remaining 1 percent contains millions of small genetic code variations that produce slightly different versions of the enzymes and other proteins that operate our bodies. These molecular variations, in combination with environmental factors, make up a person's unique "genetic profile," determining disease susceptibility and response to medications.

    With completion of the Human Genome Project in 2003, it finally became possible to read these instructions and pick out slight variations that can affect how genes function. It's still costly to scan a person's genome (the complete set of genes), but within the next few years the price tag for a readout could drop to $1,000 or less.

    Even though the vision is complicated by a host of issues – technical, economic, regulatory, ethical – personalized medicine is moving ahead on many fronts.

    "This is the real thing," says Barrett Rollins, MD, Dana-Farber's chief scientific officer and a leader of the new cancer research program. "It is by far the most complicated project I've ever worked on – and just about the most exciting."

    Others agree. "The allure and promise of personalized medicine is a powerful magnet – it represents what many of us have hoped for many years," said Sharon Levine, MD, associate executive director of the 10,000-physician Permanente Medical Group in California, during a personalized medicine conference at Harvard Medical School in November 2010.

    "It means targeting therapies for individuals based on characteristics that go beyond factors like blood type and HLA tissue matching," Levine added. "Genomic medicine promises to provide vastly greater amounts of information – but the question remains, what are we going to do with all this information to provide greater value to patients?"

    Lee Hood, a Seattle-based biotech pioneer and co-founder of Integrated Diagnostics, a personalized medicine venture, says "the new era of personalized medicine means getting vast amounts of information about a person from a single molecule or a single cell." Hood predicts that "individual genomes will become a standard of medical records in 10 years or so."

    Well before the launch of the new research program, Dana-Farber physicians were beginning to realize the potential of personalized medicine. In 2006, they began testing some lung cancer patients to identify those whose tumors had a particular gene variation that made them vulnerable to a certain "targeted" drug.

    Dana-Farber scientists have made major contributions to classifying tumors according to their genetic characteristics – not just how they looked under a microscope or the cells in which they first appeared. So, for example, breast cancers can be classified by whether they contain mutations in BRCA1 and BRCA2 genes, and whether they have an overactive gene making a protein called HER2.

    "Even earlier, Dana-Farber led the way in classifying leukemias and lymphomas by developing antibodies that identified distinctive surface markers in different subtypes," says Rollins. This approach has revealed that cancer is actually a large number of different diseases under one umbrella, observes Scott Weiss, MD, MS, director of the Partners Center for Personalized Genetic Medicine (PCPGM).

    Scott Weiss, MDScott Weiss, MD, MS, directs the Partners Center for Personalized Genetic Medicine. 

    "When [Dana-Farber founder] Sidney Farber, MD, first started treating patients with chemotherapy in 1948, there was one type of leukemia and two types of lymphoma. Today, there are 34 types of leukemia and 52 types of lymphoma [as a result of genetic classification]," Weiss points out.

    The PCPGM effort involves about 90 staff members carrying out translational research to bring the benefits of personalized medicine to patients throughout Partners HealthCare facilities. "The goal is to do for other diseases what's being done for cancer," says Weiss.

    And although the new cancer research program at Dana-Farber and BWH will involve testing appropriate patients for genetic alterations they may have inherited that could have predisposed them to cancer, the vast majority of testing will be conducted on the DNA within patients' tumor cells, rather than the DNA that is inherited.

    For this reason, cancer can be considered a special case of personalized medicine. A tumor is typically driven by genetic mistakes in body cells that occur during a person's lifetime, and for the most part, these changes aren't inherited or passed on to offspring.

    Because personalized cancer genomics has the potential to identify critical alterations that drive growth and survival of an individual's tumor, it holds great promise for improved therapy, says Geoffrey Shapiro, MD, head of Dana-Farber's Early Drug Development Center.

    "It will also help us be more intelligent about the way we choose experimental drugs for patients, and how we make new drugs going forward."

    Despite the wealth of activity in the field of personalized medicine, enthusiasts agree there are many obstacles to be conquered. Writing in a 2010 editorial in the New England Journal of Medicine, Margaret Hamburg, MD, commissioner of the Food and Drug Administration, and Francis S. Collins, MD, PhD, who led the governmentfunded arm of the Human Genome Project and is now the director of the National Institutes of Health, stated that the challenge of personalized medicine "is to deliver the benefits of this work to patients."

    For example, they said, a huge number of clinical trials must be conducted to learn the effects of gene variations on health and drug response; the vast amount of genetic data must be stored and analyzed; those findings must be translated into new drugs and extremely accurate genetic tests which will be used for major medical decisions.

    In addition, pharmaceutical companies need to be convinced there will be a sufficient market for these drugs and tests. If and when it becomes common for individuals to have their genomes scanned for DNA determinants of overall health and disease risk, questions are certain to arise about balancing the need for privacy – and protection from genetic discrimination – with the legitimate access needs of medical providers and researchers. Although some celebrities and prominent scientists have posted their genome scans openly on the Internet, many activists advocate for strict safeguards.

    The Genetic Information Nondiscrimination Act (GINA), which was signed into law in 2008, prohibits health insurers and employers from discriminating based on genetic disease predisposition. The late Sen. Edward Kennedy of Massachusetts, a state that is now considering additional safeguards, called the act the "first major new civil rights bill of the new century."

    Even in these early days, some benefits of the personalized approach to drug prescribing – known as pharmacogenomics – are already making a difference to patients.

    For example, blood-thinning drugs like warfarin (trade name Coumadin) and clopidogrel (trade name Plavix), which are taken by millions of people, can be ineffective or cause dangerous bleeding in patients who have particular variants of a drug-metabolizing gene. Identification of these genetic variants has led to new package warnings and labeling, as well as blood tests that can spot the culprit gene alterations.

    When a test for warfarin sensitivity was tested in a large clinical trial, "it led to a reduction in hospitalizations in the group that underwent genotyping for warfarin response," according to Jane Barlow, MD, MPH, a vice president at Medco Health Solutions, speaking at the personalized medicine conference at Harvard. She added, "This is a real-world outcome in personalized medicine."

    Those involved in the new cancer research program at BWH and Dana-Farber believe that in the specialized field of personalized cancer care, research-based genetic profiling of tumors may lead to "real-world" benefits before too long.

    Paths of Progress Fall/Winter 2011 Table of Contents 

  •   Email
  •   Print
  •   Share