Precision Medicine

Patients see benefits as cancer care continues to evolve.

By Susan Kreimer

Donna Lawson, 67, a retired payroll admin­istrator in Glen Rose, Texas, was diagnosed with triple-negative breast cancer—a particularly ag­gressive malignancy—in 2006. She underwent multiple surgeries, but the disease persisted. In 2011 preci­sion medicine offered a ray of hope.

Donna’s oncologist sent a tissue sample for gene sequencing at the Translational Genomics Research Institute (TGen) in Phoenix, Arizo­na. The results revealed mutations in her genome that could respond to a new oral medication being evalu­ated in a clinical trial.

The drug, BEZ-235, which Don­na received at Baylor Research Insti­tute (BRI) in Dallas, is an inhibitor targeting the PI3K pathway, which has a major impact on the growth of malignant cells and is often abnor­mally hyperactive in tumors. In the study BEZ-235 was administered in combination with chemotherapy. In Donna’s case it turned the can­cer from chemotherapy resistant to chemotherapy sensitive.

“I’ve had a year and a half of clear scans. In October it will be two years,” says Donna. “Even if the next scan doesn’t come up good, I’ve still had all this time for which I’m very, very thankful.”

Unprecedented Progress

For patients who once had dim prospects of long-term survival, precision medicine is taking the on­cology world by storm. Conquering cancer is no easy task, but research into genomics and genetics has led to unprecedented progress.

Tailored treatments have emerged to match a person’s genetic make­up or a tumor’s genetic profile. As a result, patients with cancers of the breast, lung, or colon or with mela­noma or leukemia now typically re­ceive molecular testing that guides their physicians in determining which therapies are more likely to boost the chances of survival while limiting the potential for adverse effects.

Collaborations between health­care systems and biomedical re­search companies, such as the part­nership between TGen and BRI, are helping identify specific gene defects in various disease processes that could lead to the discovery of targeted therapies for patients. In addition to cancer, research plans call for extending the positive out­comes to diabetes, infectious diseas­es, and afflictions of the cardiovas­cular, neurological, and metabolic systems.

“Precision medicine holds great promise for treatment, diagnosis of disease, and prediction of risk of developing disease,” says Rob­ert Mennel, MD, medical director of the Baylor Precision Medicine Institute and a professor of medi­cine and oncology at Texas A&M Health Science Center College of Medicine in Bryan, Texas.

“However,” Dr. Mennel adds, “while there’s a definite clinical ap­plication that’s occurring every day, much is yet to be discovered, and research is ongoing in many areas.”

Still in its infancy, precision med­icine needs to make many more strides before it can benefit the ma­jority of cancer patients. Nonethe­less, “it cannot be overstated how big of an advance it is,” says David Jablons, MD, chief of general tho­racic surgery and program leader of thoracic oncology at the University of California, San Francisco.

Customizing cancer treatment based on specific molecular ar­rangements of an individual tumor offers a much better chance of deliv­ering effective and long-lasting ther­apies that hopefully lead to a cure. “That’s a change in our thinking in general about cancer and cancer treatment,” Dr. Jablons says. “It’s been a long time coming.”

To further stimulate progress in precision oncology, President Barack Obama has unveiled the Precision Medicine Initiative.1 A $215 million investment in the pres­ident’s 2016 budget will provide funding for the National Institutes of Health (NIH), along with the US Food and Drug Administration (FDA), and the Office of the Na­tional Coordinator for Health In­formation Technology (ONC). The initial announcement came during the State of the Union address in January 2015, with specific details disclosed 10 days later.

Of this sum NIH will obtain $130 million to develop a national cohort of 1 million or more Ameri­cans to voluntarily participate in re­search. The National Cancer Insti­tute (NCI), part of NIH, will receive $70 million to accelerate efforts in identifying genomic drivers in can­cer and applying that information to better therapies.

A $10 million allotment to the FDA will pay for modernized data­bases that protect participants’ pri­vacy, as well as new strategies for assessing the accuracy and reliabil­ity of gene-sequencing technology tests. ONC will use the remaining $5 million to support the develop­ment of interoperability standards and requirements that address pri­vacy and enable secure exchange of data across systems.

“Oncology is the clear choice for enhancing the near-term impact of precision medicine,” wrote Francis S. Collins, MD, PhD, current NIH director, and Harold Varmus, MD, who held directing posts at NIH and NCI, in the February 2015 is­sue of the New England Journal of Medicine.2

“Cancers are common diseases; in the aggregate, they are among the leading causes of death nationally and worldwide, and their incidence is increasing as the population ages. They are also especially feared, be­cause of their lethality, their symp­toms, and the often toxic or disfig­uring therapies used to treat them,” the co-authors continued. “Re­search has already revealed many of the molecular lesions that drive cancers, showing that each cancer has its own genomic signature, with some tumor-specific features and some features common to multiple types.”2

The Personal Impact of Precision

Jeanine Pucci, now 44, a first-grade teacher from Howard Beach, New York, was scheduled to receive che­motherapy for Stage IV lung cancer in December 2013, when lab results revealed she had the ALK gene al­teration, which is present in 3 to 5 percent of people with non–small cell lung cancer (NSCLC). Unlike the hereditary BRCA1 and BRCA2 mutations that may be present in patients with breast cancer, this is an acquired alteration that occurs in some malignant cells as cancer develops.

The discovery of her ALK gene alteration has offered Jeanine two new, productive treatments since that initial result. From December 2013 to March 2015, she took the oral medication Xalkori® (crizotinib; targeted therapy)—granted acceler­ated approval by the FDA in August 2011 for patients whose metastatic NSCLC expresses the ALK gene al­teration. When she became resistant to Xalkori, she turned to the oral drug Zykadia® (ceritinib; targeted therapy), approved in April 2014, also for ALK-positive advanced NS­CLC, which shrunk the tumor in her liver to less than half its size.

Although Jeanine has experienced some side effects, including diarrhea, vomiting, and elevated liver enzymes, the two drugs have afforded her pre­cious time. When she was initially diagnosed, she remembers, “An on­cology nurse said to get my affairs in order—that this was going to kill me.” Now, two years later, Jeanine, a lifelong nonsmoker, is grateful for these advances in treatment: “With­out these therapies I don’t think that I would be alive right now,” she ad­mits. “I know that.”

Jeanine emphasizes the need for continued research to help patients for whom precision medicine is not suitable—for example, when a tu­mor lacks a specific genetic abnor­mality that responds to a matching drug, or who become resistant, as in her case. “I wish they would find something that would work forev­er,” she says. “These targeted ther­apies work for about eight to 10 months. The cancer learns to kind of trick the pill; it outsmarts the medication. That’s why I had the progression.”

Benefits of Precision Medicine’s Targeted Therapies

For those who respond to precision medicine, the treatments can greatly extend survival and improve quality of life. Patients tend to tolerate the therapies well, avoiding the com­mon side effects such as hair loss and lower blood counts that arise with chemotherapy, says Saiama Waqar, MD, a thoracic oncologist and an assistant professor at Wash­ington University School of Medi­cine in St. Louis, Missouri.

“Hair loss can be pretty emotion­ally devastating,” Dr. Waqar says, “and decreased blood counts may lead to severe infections and even increase the risk of death.” In con­trast, diarrhea and rash are the main side effects of Tarceva® (erlotinib), the most common targeted therapy for lung cancer, and can often be well-managed with medications.

Tumor shrinkage from drugs targeting the EGFR and ALK gene alterations can help alleviate short­ness of breath and reduce reliance on supplemental oxygen, Dr. Waqar says. Taking a pill at home is also more convenient for patients than receiving chemotherapy infusions in a hospital or outpatient facili­ty, resulting in fewer medical ap­pointments. The convenience and reduced hospital time, Dr. Waqar says, have another benefit: “Pa­tients often can continue to work and have as close to a normal life as possible.”

In Dr. Waqar’s assessment, many benefits of the treatments that fall under the umbrella of precision medicine combine to offer patients something intangible—and invalu­able—on their journey with cancer: control. “That’s a pretty empowering feeling for patients,” she says.

Women and Lung Cancer
As a lung cancer survivor, Jeanine Pucci has been fortunate to benefit from the advances in precision medicine, but many women are not so lucky. Lung cancer is the leading cause of cancer-related death, and less than half of all women and men diagnosed with lung cancer are alive one year after diagnosis.

Lung cancer strikes female nonsmokers more frequently than male nonsmokers. Jeanine, who never smoked, was diagnosed with advanced lung cancer in her early forties, after experiencing a bad cough, a sharp pain in her back, and fatigue. Nonsmokers are less likely to be diagnosed in an early stage because no one suspects that cancer is lurking in their lungs. Adenocarcinoma—a type of non-small cell lung cancer that afflicted Jeanine—is also slightly more common in women than other forms of lung cancer.

The good news is that, like Jeanine, other women may test positive for a molecular marker that could respond to corresponding targeted therapies. To help raise awareness about lung cancer, Jeanine has joined the American Lung Association’s national initiative LUNG FORCE. Learn more about the organization’s efforts at


  1. Fact Sheet: President Obama’s Precision Medicine Initiative. The White House web­site. Available at: the-press-office/2015/01/30/fact-sheet-presi­dent-obama-s-precision-medicine-initiative. Ac­cessed July 2, 2015.
  2. Collins FS, Varmus H. A new initiative on precision medicine. New England Journal of Medicine. 2015;372(9):793-95. doi: 10.1056/NE­JMp1500523.