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What’s the Big Idea? Cancer Leaders to Talk Precision Medicine

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In a few weeks, top minds in the city and state will gather to discuss one of the hottest cancer topics in healthcare: precision medicine.  It’s a term many have heard, seen on a billboard, or even experienced, but what does the omnipresent buzzword really mean today—and for tomorrow?

For the first time, the American Association for Cancer Research (AACR) and the Philadelphia Inquirer are hosting a “town hall” of sorts that will bring together directors from cancer centers, including Abramson Cancer Center (ACC) director Chi Van Dang, MD, PhD, and other experts and doctors firmly planted in this world to help bring the answers to these questions into better focus and share their “big ideas” about personalized approaches to prevention and treatments. 

“Here we are at the beginning of a new year, in the wake of good news about the bump in funding to the National Institutes of Health and secured funding for President Obama’s Precision Medicine Initiative, two key actions that will help this area of medicine soar,” said Dang, who will serve as a panelist at the event, taking place at the College of Physicians of Philadelphia on January 21. “This is an important time for precision medicine, so it makes good sense for us come together to discuss both the successes, pitfalls and what’s next.”

The prospects of the President’s initiative, a nationwide study set to enroll over one million people, are promising, but let’s take a moment and remember the host of precision medicine efforts out there already—many happening right here at Penn Medicine and likely to come up at the AACR/Inquirer event.

Your Cancer’s Makeup

Penn’s Center for Personalized Diagnostics (CPD), which recently named Kojo S.J. Elenitoba-Johnson, MD, as its founding director, is diving deeper into cancer patients' tumors with next generation DNA sequencing.

The genetic tests help refine diagnoses with greater precision than standard imaging tests and blood work by spotting known mutations that can inform the treatment plan. Since it launched in February 2013, the CPD has performed more than 4,000 advanced diagnostics, representing a wide range of cancers.  It’s also producing actionable findings: Of those tests, 75 percent found disease-associated mutations, revealing possible new treatment pathways.

This new CPD video helps breakdown how the process works, but a patient story can really help connect the dots. We’ve written about several people who benefited from the CPD, including one acute myeloid leukemia patient with an FLT3 mutation that made her a candidate for a targeted therapy, and another whose cholangiocarcinoma was successfully treated with a BRAF-targeted therapy after the mutation—typically associated with melanoma—was spotted. 

ACC’s role as a national leader in personalized cancer care was also reinforced with the opening of the Center for Rare Cancers and Personalized Therapy in 2015.

Directed by Marcia Brose, MD, PhD, this virtual center enrolls patients into clinical trials based on genetic markers rather than tumor origin.  Patients with the same mutation, BRAF for instance, but different cancers, are part of the same clinical study investigating a targeted therapy.  A story, set to air on TV news affiliates across the country in the upcoming weeks, will feature a patient with a rare salivary tumor who ran out of treatment options, until a HRAS mutation identified through the CPD put him back on track, after switching to the drug tipifarnib. The patient responded well, and a recent scan revealed that his disease has stabilized.

Last year, the ACC also launched the Center for Precision Surgery, led by Sunil Singhal, MD, an assistant and director of the Thoracic Surgery Research Laboratory, to deploy live molecular imaging in the operating room to help remove lung, brain, and prostate cancers using an injectable dye that has been specially engineered to accumulate in cancerous tissues, much more so than normal tissues. This technique, if approved by the U.S. Food and Drug Administration, may offer great promise to physicians – a strategy that could allow greater accuracy in removing the entire tumor.

The Basser Center for BRCA is another mainstay at Penn Medicine. The only center in the world solely devoted to BRCA-related cancers, the Basser Center supports cancer care and BRCA research at every stage, including communication, outreach and risk assessment, prevention, early detection, treatment, clinical trials, and survivorship.

A recent study from Basser involved multiplex genetic testing, which allows for the simultaneous analysis of alterations in 25 cancer-related genes.  The testing is hotly debated among experts in cancer research as some argue the limited amount of information available for some of the mutations may cause increased and potentially undue anxiety for patients. However, Basser researchers found that many BRCA 1/2-negative patients choose to proceed with comprehensive testing for genetic mutations that increase cancer risk, and when presented with counseling before and after testing, most make informed decisions and experience decreased levels of anxiety.

Immunotherapy Likely to Take Center Stage

Working with the Basser Center, Robert Vonderheide, MD, DPhil, the Hanna Wise Professor in Cancer Research, is leading a trial investigating a vaccination to prevent BRCA1/2-related cancers. As a first step toward this overall goal, the study will work to determine the clinical impact of vaccinating high-risk patients in remission using a DNA cancer immunotherapy that targets a human telomerase reverse transcriptase (hTERT) gene, which is known to be associated with many cancers. The vaccination approach was developed by David Weiner, PhD, a professor of Pathology and Laboratory Medicine, whose innovative DNA vaccination strategy reduced pre-malignant cervical tumors in a recently published clinical trial.

Brian J. Czerniecki, MD, PhD, the co-director of Penn’s Rena Rowan Breast Center, also developed dendritic cell vaccines, made with the patients’ own white blood cells, for the treatment of cancer and is involved with several ongoing clinical trials for treating patients with early breast cancer.

Another immunotherapy clinical study by Amit Maity, MD, PhD, a professor of Radiation Oncology, and Andy J. Minn, MD, PhD, an assistant professor of Radiation Oncology, known as the “RadVax” trial, is combining newer checkpoint inhibitor drugs, also known as PD-1 drugs, with radiation therapy. The Penn team found that combining the immunotherapy ipilimumab with radiation therapy was safe and shrank tumors in metastatic melanoma patients. It is believed that the radiation helps boosts the immune system’s attack on the disease. The trial is among other immunotherapy trials at Penn using PD-1 drugs for melanoma and other cancers, such as mesothelioma.

But the immunotherapy work under ACC’s director of Translational Research Carl June, MD, and Bruce Levine, PhD, who both serve as professors in Pathology and Laboratory Medicine, is perhaps Penn’s most well-known of precision medicine approaches—and one of the projects to be highlighted at the event.

Stephan Grupp, MD, PhD, a professor of Pediatrics at the Perelman School of Medicine at Penn and director of Translational Research in the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia, and Tom Whitehead will be speaking about the investigational cellular therapy CTL019 studies, and sharing Tom’s daughter’s, Emily Whitehead, story, which was recently covered by NBC Nightly News. She remains cancer free after receiving the therapy, which used her own T cells to hunt down and kill her acute lymphoblastic leukemia. 

“Philadelphia is a hotbed for healthcare innovation and groundbreaking scientific research—which becomes even more apparent as the ACC continues to move the needle in the precision medicine world,” Dang said.  “Quickly evolving diagnostics and genetic tests, cancer vaccines, and powerful personalized therapies that use the body’s own immune system to fight off cancer: These are just a few of the medical advances being utilized today that are giving patients the greatest chance.”

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