Molecular Matrix
Pharmacogenomics—or targeted medicine—places health care at the cusp of a revolution in personalized treatments, career opportunities and new ethical issues

By Cathryn Domrose
July 2, 2003

Imagine a day in the not-so-distant future when, in addition to taking temperatures, checking blood pressures and noting oxygen saturation levels, you scan your patients' genetic information from a computer microchip.

This information, interpreted by a superfast computer, tells you if your new cancer patient metabolizes certain medicines quickly, normally or slowly. It tells what medication works best for her high blood pressure. It indicates whether her breast cancer will best respond to standard treatment or to a new drug on the market, and whether she is in a high-risk category for other cancers triggered by certain environmental factors like cigarette smoke or air pollution.

You work with a pharmacist and physicians to administer doses of medication based on genetic information that shows how your patient responds to them. Your cancer patient slowly metabolizes the cancer drug shown to work best for her. She will start off with low doses to reduce the side effects of toxic drugs lingering in her system. But she metabolizes pain medications quickly and may need more frequent doses of painkillers to stay comfortable.

You explain to her children why their mother is receiving a lower dose of the cancer drug than an aunt on the same medication. You explain why this therapy has a better chance of working, based on their mother's individual genetic profile, than a different drug they read about on the Internet.

You work with the patient and her family to draw up a health plan based on certain environmental indicators shown by her genetic information. For instance, she seems to be susceptible to stress and should take care to avoid situations that might exacerbate her illness or increase chances of a recurrence. You recommend testing for family members to see whether they also have indicators that should be watched-or even blocked with early intervention medications based on their own genetic information.

The children wonder if they should share this information with other relatives. They also are concerned about how this might affect their own health insurance-would it be considered a pre-existing condition? You explain the privacy laws that cover genetic information and discuss ways they could alert other family members without unduly alarming them.

Thanks to your explanations, the patient and her family feel much more relieved about the new therapy.

Some details of this marvelous medical scenario-the microchip containing detailed genetic information, for instance-are still at least 10 years and perhaps many more years away, those who work in genetics say. Others, such as genetic information that helps determine what blood pressure medicine to take, may arrive within a few years. Some are happening as you read this: Patients across the country are receiving medicines targeted to their illnesses and genetic makeup.

In the world of medical therapies, one size no longer necessarily fits all.

What does this mean for nurses? Nurses already are involved as researchers for genetically targeted tests, drugs and procedures, and the demand probably will rise as the need for more research and clinical trials increases, those who work with pharmaceutical companies say. Nurses already may be dealing with patients' questions about genetically targeted therapies and tests in clinical trials or already on the market.

As targeted medicine moves to the clinical setting, nurses will need to learn the language of genetics and to think at a molecular level in order to explain new therapies to patients, families and communities. Nurse practitioners who prescribe drugs will need a basic understanding of genetics and research to keep up with the latest findings.

As individual genetic information and what it means becomes increasingly available, nurses will be able to use it as another tool to help their patients better understand their illnesses and responses to treatments. But they also will have to deal with new implications of old ethical issues, including privacy, access and distribution of new therapies.

"It's analogous to the discovery of penicillin," said Agnes Masny, MSN, MPH, NP, RN, a nurse practitioner specializing in cancer risk assessment at the Family Risk Assessments Program at the Fox Chase Cancer Center in Philadelphia. "The genomics era is going to change the way we practice medicine and nursing."

Informed choice. Of all the medical breakthroughs promised by the rapidly moving field of genetics, targeted medicine-also known as personalized medicine or pharmacogenomics-is the one most likely to be used soonest on a large scale, leaders in the field of medical genetics agree. Constantly emerging discoveries linking genetic variations to physiological reactions and increasingly powerful and sophisticated computers that can analyze and categorize this information have opened up a new universe to drug researchers.

Almost all pharmaceutical companies have some form of pharmacogenomic research department. Some targeted therapies-especially in oncology-already are being used and more are expected soon to treat diseases like hypertension, diabetes and mental illness.

Today, much conventional drug therapy is hit-or-miss educated guessing. Physicians assault a tumor with an arsenal of chemotherapy and hope the barrage wipes it out without destroying too many healthy cells. Or they give a standard dose of anti-depressants that probably will need to be adjusted based on patient response.

"There are so many drug choices for hypertension," said Mary Engler, Ph.D., MS, RN, professor and director of the cardiovascular and genomics graduate programs in the department of physiological nursing at the University of California, San Francisco.

These include various diuretics, calcium channel antagonists, beta-blockers, ACE inhibitors, alpha-adrenergic blockers and angiotensin II receptor antagonists, she said. Some drugs may not work or may work only in higher doses. Some patients may not metabolize the drug well and be at risk for its toxicity. Some may have an inherited defect that can alter normal response to medication.

"How are [the proper drugs] selected?" Engler asked. "There are certainly guidelines; however, selecting optimal medications and dosages can be trial and error at best."

Targeted medicine takes a more evidence-based approach, although in its present state, it is still far from a sure bet. A classic example is Herceptin (trastuzumab), a drug that targets a protein involved in a certain type of breast cancer. Herceptin blocks the growth of tumor cells spurred by overabundance of a gene called Her2. About 30 percent of breast cancer patients have this condition. Herceptin seems to help about half the patients who take it.

In combination with other therapies, tests show Herceptin keeps tumors under control for up to 17 months. But, perhaps most important, because the drug targets only cancerous cells, it has considerably fewer side effects than traditional chemotherapy. Patients do not experience nausea, hair loss, exhaustion or other symptoms that can make the cure seem worse than the disease.

Besides providing clues to choose the best drug to fight a particular disease, genetic markers also can predict how various people respond to various drugs-how the drugs are absorbed, metabolized, distributed and eliminated. Researchers are looking closely at the anticlotting drug warfarin, used to treat heart patients. They have found genetic differences to account for the way various patients respond to the drug and why some experience dangerous bleeding at what seems a normal dose.

The Swiss-based pharmaceutical company Roche announced in May that it planned to launch a genetic test that would determine a patient's metabolic status as a guide to prescribing drugs and doses, Reuter's News Service reported. Roche's division head, Heino von Prondzynski, told Reuter's the test eventually could be used to screen all newborns to show whether there were certain drugs they should never be given.

"The escalating numbers of serious adverse drug reactions and drug-related morbidity and mortality, as well as the associated costs, are accelerating the progress of pharmacogenomics," Engler said. Depending on how the statistics were interpreted, adverse reactions to drugs were the fourth or sixth leading cause of death in the United States in 1998.

Herceptin, approved in 1998, was developed specifically as a result of genetic research. Although other new drugs targeted at specific diseases will continue to be developed, most early-stage targeted medicine most likely will involve therapies already on the market.

Diagnostic testing probably will comprise much of the first phase of genetically targeted medicine, pharmacogenomic researchers say. At first, it probably will not be cost-effective to test people for every medication, even if tests are available, said Cynthia Prows, MSN, RN, a clinical nurse specialist in genetics at Cincinnati Children's Hospital Medical Center.

Early testing may be limited to drugs that have a narrow therapeutic range, are highly toxic or costly, she said. But eventually, many who work in genetics predict, the tests could become as routine as blood sugar or cholesterol screenings.

"I think the day will come when before anybody gets a drug, there will be a test to determine how you will respond to it," said Steven Seelig, MD, Ph.D., divisional vice president of research and development and chief medical officer for Vysis Inc., the Chicago company that developed Herceptin.

Genetic information eventually may allow health care workers to target medical procedures and lifestyle interventions, as well as medicines. Researchers are looking for a correlation between genetic markers and the way patients respond to stents, said Lorraine Frazier, DSN, NP, RN, associate professor at the University of Texas Health Science Center at Houston School of Nursing, who is researching genetics and markers of cardiovascular disease. Similar information may predict how environmental factors like stress and diet affect-or don't affect-physical conditions.

"Do all patients with high blood pressure need to decrease their salt intake? Probably not," Frazier said. "We used to give patients guidelines that were ineffective, that probably affected their quality of life. In the future, we'll look at the patient genetically and physically."

Growth industry. Although no one can say when targeted medicine will become commonplace, everyone agrees that the health care workforce needs to prepare for it now. "The current estimates are three to five years before widespread application of pharmacogenomics occurs," Engler said. It is imperative, she said, that nurses have a basic understanding of pharmacogenetics "and genetics, for that matter. We need to keep pace with the explosion of new knowledge."

Linda McAllister, MD, Ph.D., director of medical genetics for Celera Diagnostics in Alameda, Calif., sees an immediate need for nurses with a good understanding of genetics in the research field, as pharmaceutical companies scramble to search for new diagnostic tests and therapies that can be targeted to certain genetic variations. "The research aspect is potentially a huge opportunity for nurses," she said. "In a way, it's a kind of career opportunity and a growth industry for this area. We will need to do clinical research on a very large scale."

As more genetically targeted therapies come onto the market, nurses will need to be able to explain how they work to patients, said Dale Halsey Lea, MPH, RN, assistant director of the Southern Maine Genetics Services Foundation for Blood Research in Scarborough, Maine. They will need to explain that the targeted therapies are something new, that patients may have different responses to them and that long-term effects and possible side effects have not yet been evaluated.

Nurses also will need to educate patients about genetics and about how they may have a condition or gene variation that is or isn't responsive to a particular therapy, Halsey Lea said. Parents of children with cancer frequently compare types and doses of medicines their children are taking, Masny said. They also use the Internet and research available therapies. Nurses will have an important job in helping them to understand how each patient's therapy is personal and not necessarily exactly the same as for other people who have the same illness or who are taking the same drug.

"This stuff is complicated and it's difficult for people to understand. A lot of doctors don't understand it," Seelig said. "If I were a leader in nursing, I would get nurses to be the primary educators of genetic content information, to know the language of genetics and how to communicate it to patients. That's a way nursing could reassert control of the profession in the health care industry."

Understanding the relationship between genetics and medications also may help nurses better understand their patients' needs, especially for pain medication. Research suggests that between 1 percent and 10 percent of the population are ultra-rapid metabolizers. Genetic tests eventually may determine who metabolizes pain medication more quickly and what kinds of pain medications are most effective.

"It's not just the same as a standardized approach to pain medication, where everybody who has pain is going to have codeine," Halsey Lea said. A genetic explanation for why certain patients are always asking for pain medication may allow nurses to see them in a more sympathetic light, Masny said.

Questions and quandaries. Although testing to see how a patient reacts to a drug has different ethical and social implications from testing to see whether a patient has an incurable disease, nurses still will have to be prepared to deal with potentially devastating emotional blows, Prows said. "What happens if a patient has a test done and results indicate only a few drugs or no available drugs will work? That's going to be some tough counseling."

Or what if genetic tests for drug efficiency in combating a certain illness show something unexpected, like a marker for a completely different disease, she asked. A similar scenario already has occurred, she said, when a genetic test for heart disease risk later was discovered to reveal an increased risk for early-onset Alzheimer's disease.

"Now what do you do?" she asked. "Do you call those people back who thought they were being tested for cardiovascular risk? Should you tell them about the possible risk for Alzheimer's disease?"

Nurses also will have to discuss whether and how their patients should share information with family members. If a patient responds positively or negatively to a therapy because of genetic makeup, other family members may have the same response and could benefit or be harmed in the future from the therapy, Halsey Lea said. "How does that fit into the issue of patient privacy?" she said.

Health care workers also will have to grapple with questions and scenarios regarding access and payment for the new therapies. Just because new tests and therapies come on the market doesn't mean they will be available to everyone, Halsey Lea said. Many people can't afford new medications now, let alone the cost of a test. AIDS has shown that complicated, disease-targeted therapies are expensive and not always easy to obtain.

The age-old health care question of who pays for what will spawn new ethical issues. Can insurance companies require patients to have a test to show they would be genetically responsive to a particular therapy before authorizing payment? Will patients feel coerced into testing? What if the patient doesn't genetically respond to any therapy or wants to try one that genetic markers predict won't work? Or what if tests show a treatment may add a few months to their lives, but won't help them in the long run?

"Being prepared and thinking about the possible limitations is important," said Janet Williams, Ph.D., RN, a nursing professor at the University of Iowa and past president of the International Society of Nurses in Genetics. "Educators need to prepare the nursing workforce to understand what individual genetic medication profiles might be and to prepare nurses to use them in patient care regarding medication selection, education and monitoring, and to think of ways to protect the public against possible abuses."

Nurses also must understand and be prepared to explain that targeted medicine, with all its exciting potential, will never be the solution to all medical problems, nor will it affect or change a lot of the things nurses do, those who study genetics say.

Nurses will continue to take vital signs, ask questions, talk to patients and families and assess conditions. Genetic information will just add one more piece to the picture. "All that [nurses do] is still going to be there," Seelig said. "It's just going to be more complicated."

The integration of genetic information into health care represents broad possibilities for disease management, including risk assessment, diagnosis, detection and treatment, said Paula Trahan Rieger, MSN, RN, director of international affairs for the American Society of Clinical Oncology and immediate past president of the Oncology Nursing Society. But, she said, she does not believe that targeted medicine will significantly change basic nursing care. "The skills that nurses have in caring for people will transcend whatever therapies we see in the future," she said.

Frazier noted that Florence Nightingale focused on her patients' environment, opening windows in a room to let in air and light. "We will continue to do that, only with different tools," she said. "We will use molecular tools in the future."

Contact Cathryn Domrose at kaguilar@well.com