Curated Cancer Careby ANNA WILLIAMS | photography by LAURA BROWN
Physicians and scientists in OncoSET are teaming up to help pioneer precision oncology.
Until recently, treatment for patients with cancer generally followed a broad-brush, one-size-fits-all approach. Today, it is recognized that each cancer — just like each patient — is unique.
Armed with the understanding that distinct genetic mutations and abnormalities are at the root of every patient’s cancer, physicians and scientists now aim to usher in an era where treatment is truly tailored to the individual. The hope is that providing therapies targeted to the specific genetic drivers of cancer will reduce the toxic side effects seen in less precise treatments and offer patients improved outcomes overall.
Such is the case with Chuck Maniscalco. In the fall of 2016, Maniscalco, a retired Chicago business executive in his 60s, was diagnosed with Stage IV lung cancer — a disease his mother and younger sister both died of years earlier.
In the past, his treatment options would typically have been limited to standard chemotherapy. But after receiving genetic testing at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Maniscalco learned he had a mutation in the epidermal growth factor receptor (EGFR), which can fuel cancer growth. As a result, he was a candidate for Tarceva (erlotinib), an oral medication that specifically targets the activity of the EGFR protein.
“I am the beneficiary of research, pure and simple. By all rights, I shouldn’t be alive, much less up and at it every day,” said Maniscalco, a year and a half after his diagnosis. “The team of people who are caring for me at the Lurie Cancer Center are fabulous, but it is the research that led to targeted treatments that is the key to my life.”
This is the potential of precision oncology, and the premise of OncoSET, the flagship clinical and research program at the Lurie Cancer Center. First launched in 2015, OncoSET is the Lurie Cancer Center’s entry into the emerging movement of precision medicine. Through an innovative three-step process — Sequence, Evaluate, Treat — the clinic couples oncology with genomic sequencing to offer cutting-edge cancer care personalized to each patient.
“This is really the most advanced form of oncology,” says Amir Behdad, MD, assistant professor of Pathology, director of Cancer Molecular Diagnostics and co-director of OncoSET’s Molecular Tumor Board. “If we can attack only a target that’s unique to a patient’s tumor cells — as opposed to globally attacking the body with chemotherapy — that’s a really attractive option.”
This strategy, Behdad notes, has only recently become possible thanks to advances in genetic technology. Next-generation sequencing has now enabled scientists to obtain a robust understanding of the genetic profile of tumors, which had previously represented a significant challenge. With more knowledge of the molecular makeup of tumors, therapies designed to target specific tumor markers have since followed.
“We created OncoSET because science and technology are driving big changes in the way we treat cancer, and as the leading cancer center in Chicago, we thought we should offer precision medicine to our patients first,” says Leonidas Platanias, MD, PhD, director of the Lurie Cancer Center. “I believe very strongly that this is the way medicine will be practiced 10 years from now.”
Above: Massimo Cristofanilli, MD, director of OncoSET, the Lurie Cancer Center’s flagship clinical and research program built around the emerging movement of precision medicine.
“I am the beneficiary of research, pure and simple. By all rights, I shouldn’t be alive, much less up and at it every day. The team of people who are caring for me at the Lurie Cancer Center are fabulous, but it is the research that led to targeted treatments that is the key to my life.”
Lung cancer survivor
A Clinical Program, Informing Tomorrow’s Cures
In addition to helping individual patients, there’s another, broader, benefit to the OncoSET model: By collecting and analyzing extensive genomic data, OncoSET informs ongoing discovery of targeted cancer drugs and helps advance pre-clinical research at Feinberg and around the world.
“There were a couple of major goals we wanted to accomplish very quickly,” says Massimo Cristofanilli, MD, director of OncoSET and associate director for Translational Research at the Lurie Cancer Center. “One, of course, was to be more precise in treatment planning for patients and establish the clinical service. But at the same time, we also wanted to advance translation and feed our research purpose.”
The OncoSET process begins with a simple blood draw from a patient for a liquid biopsy (in some cases, a traditional tissue biopsy is available as well). Through collaborations with commercial partners for genetic testing, OncoSET leverages next-generation genomic sequencing to pinpoint changes in specific genes and produce a comprehensive profile of a patient’s tumors. (OncoSET is currently focused on analyzing solid tumors, but will soon also evaluate hematologic malignancies, such as lymphoma and leukemia.)
“We’ve created the first clinic in Chicago — and one of only a few in the country — where it doesn’t matter where the tumor is located. What matters now is the composition of the tumor and the patient’s genomic analysis,” explains Platanias, who is also the Jesse, Sara, Andrew, Abigail, Benjamin and Elizabeth Lurie Professor of Oncology.
The OncoSET Process
Through an innovative three-step process, the Lurie Cancer Center’s flagship clinical and research program offers cutting-edge cancer care personalized to each patient.
STEP 1: SEQUENCE
profile the tumor
STEP 2: EVALUATE
evaluate the results
STEP 3: TREAT
treat with targeted therapies
Every week, OncoSET’s Molecular Tumor Board gathers to analyze the sequencing results of individual patients, one by one.
During this evaluation stage, it’s all hands on deck: The multidisciplinary team, co-directed by Cristofanilli and Behdad, is made up of medical, surgical and radiation oncologists, along with pathologists, molecular scientists, pharmacologists, radiologists, genetic counselors, bioinformaticians and other experts across a range of specialties.
Informed by the tumor’s unique profile, the team devises an optimal treatment plan for each patient. That treatment, based on the molecularly defined targets, might include an available drug or enrollment in an early-stage clinical trial being conducted at Northwestern.
Since its inception, the Molecular Tumor Board has evaluated the genetic profiles of hundreds of patients, many of whom had advanced stage cancer or cancer that was unresponsive to standard treatment. Not only has the model made a real difference in individual patient outcomes, but with basic scientists at the table, new insights gleaned through the clinic may eventually serve as the building blocks of tomorrow’s targeted cures.
“After doing these gene profiles and analyses of patients, we can bring all that information back to the lab,” Platanias explains. “We can try to better understand some of the abnormalities we detect — we still don’t know the importance of many — conduct more studies, develop new drugs and, eventually, bring them back to the clinic.”
Pioneering a Future of Precision Oncology
OncoSET has also emerged as a national leader in advocating for a precision medicine approach to cancer care and research.
“One important focus for this program is educating physicians on the value of this model,” says Cristofanilli, also a professor of Medicine in the Division of Hematology and Oncology. “We want to be on the forefront in demonstrating its utility.”
With that mission in mind, OncoSET hosted its inaugural symposium last spring, sharing significant advances in precision oncology with healthcare professionals from across the country and discussing strategies for translating new discoveries into clinical practice. The Second Annual Lurie Cancer Center OncoSET Symposium: Practical Applications of Precision Medicine will be held May 17, 2018.
Cancer leaders at the inaugural OncoSET Symposium last spring.
In OncoSET, patients are also enrolled in a prospective registry study — now totaling more than 400 entries — which provides a rich database for basic scientists investigating particular mutations. The team is actively working on developing retrospective analyses of treatment outcomes.
“We coordinate our data with other institutions all over the country. Eventually, after enough information has accumulated, there will be a tipping point — really a drastic change — in the way we practice oncology,” says Platanias, also a professor of Medicine in the Division of Hematology and Oncology, and of Biochemistry and Molecular Genetics.
This new approach to oncology is still at an experimental stage, of course, and the OncoSET team notes that as science and technology in this area rapidly evolve, so will the process of providing precision cancer care. The program is currently centered on genomics and molecular diagnostics, but in the future new tools like epigenetic analysis, proteomic analysis and metabolomics may also help match patients with the individualized treatment plan that might benefit them most.
“The more we understand in science, the more we will be bringing it back to OncoSET to optimize our analysis,” Platanias adds. “We think this is the future, and we are moving fast.”
To refer a patient or request a consultation, email OncoSET@northwestern.edu or call 312-472-1234.