News from Around the Cancer Center
June 2, 2016 | Dagny Stuart
A possible targeted therapy emerges for triple-negative breast cancer
A targeted therapy for triple-negative breast cancer (TNBC), the most aggressive form of breast cancer, has shown potential promise in a recently published study. TNBC is the only type of breast cancer for which there are no currently approved targeted therapies.
The new study led by Vanderbilt-Ingram Cancer Center (VICC) investigators has identified gene alterations that may explain why TNBC is resistant to most existing treatments, and suggests that a targeted therapy currently in clinical development may prove beneficial.
The research, led by first authors Justin Balko, Ph.D., Pharm.D., and Luis Schwarz, M.D., was published online April 19, 2016, in Science Translational Medicine.
While chemotherapy prior to surgery can eradicate TNBC in approximately 30 percent of patients, in other patients the cancer behaves in a manner resistant to chemotherapy and often spreads or metastasizes to distant sites in the body, at which point there is no proven cure.
The JAK-STAT gene-signaling pathway, which is critical to cell growth and survival, drives the growth of many tumors, including breast cancer. Scientists have not been able to identify clear-cut drivers for TNBC but there has been some evidence that the JAK2 gene may play a role.
For this study the authors studied tumor samples from 111 patients treated at the Instituto Nacional de Enfermedades Neoplásicas (INEN), in Lima, Perú. After sequencing the tumor samples, the authors found that the JAK2 gene was more frequently amplified in chemotherapy-treated TNBC than in tumors before treatment. These patients with JAK2 gene-amplified tumors also had a recurrence of their cancer sooner and were more likely to die within 20 months following surgery.
These findings suggested a potential causal role for JAK2 in drug resistance.
The investigators also found that JAK2 increased in a limited number of patients where biopsies were collected at different times during treatment. The rate of JAK2 amplification in these tissues was similar to samples obtained after chemotherapy, suggesting that JAK2 plays a supporting role in drug resistance and cancer stem cell-like features.
In cell lines, the researchers first tested ruxolitinib, a general JAK inhibitor, but it did not block tumor formation in the JAK2-amplified cells.
The researchers then turned to a JAK2-specific inhibitor now known as BSK805, which markedly reduced TNBC tumor growth in mice when paired with chemotherapy.
The findings suggest a role for JAK-2 inhibitors for these triple-negative breast cancers.
Support for the research included funding from the IBC Network Foundation, U.S. Department of Defense and the National Cancer Institute.
– by Dagny Stuart
Singer’s concert honors care received at Vanderbilt-Ingram Cancer Center
A cancer patient’s gratitude toward his Vanderbilt-Ingram Cancer Center (VICC) physician led to a star-studded concert to benefit the Cancer Center.
Colon cancer survivor and country artist Wade Hayes was joined by six-time CMA and ACM Female Vocalist of the Year Miranda Lambert, four-time Grammy and CMA Award-winning artist Steve Wariner and Kix Brooks, CMA and ACM Award-winning artist of country duo Brooks & Dunn and co-host of “American Country Countdown,” for the concert that was held at the Franklin Theatre in Franklin, Tennessee.
Hayes was 42 when symptoms including abdominal pains and bleeding became too severe to ignore.
A colonoscopy revealed that the singer best known for the No. 1 hit “Old Enough to Know Better” had advanced (stage IV) colon cancer.
One of Hayes’ physicians was Jordan Berlin, M.D., Ingram Professor of Cancer Research and co-leader of the Gastrointestinal Cancer Research Program at VICC. After three years of treatment, tests showed Hayes was cancer free and Berlin told him to “Go live your life.” Hayes found inspiration in the advice, penning a song “Go Live Your Life,” which is also the name of his latest album.
Berlin said he was touched by Hayes’ decision to headline a benefit concert with proceeds earmarked for the VICC GI Oncology Program.
– by Dagny Stuart
Professor designs special apron for breast cancer patients
A Vanderbilt professor has designed a special apron for breast cancer patients after first-hand experience dealing with chest drainage tubes following surgery.
Craig Anne Heflinger, Ph.D., professor of Human and Organizational Development at Peabody College, based her design on the big-pocketed aprons worn by employees at The Home Depot. A friend gave her one of those aprons when she came home from Vanderbilt University Medical Center (VUMC).
“They are great,” Heflinger said. “They’re functional, but they tie in back.”
A knot behind the back can be uncomfortable for people recovering from breast cancer surgery, who have to sleep on their backs and contend with drainage tubes for up to three weeks.
“I thought, ‘I can make a better drain apron than this,’” Heflinger said.
So she fashioned one with an adjustable, side-fastening alternative.
“It needs to be something washable because your chest drains leak a little bit,” she said. “I like having something colorful and silly because you are feeling so bad. I think I made my first one out of Tennessee Titans fabric.”
She shared the apron pattern with the Vanderbilt Sewing Club, whose members began making them for other patients. For Christmas 2014, she asked her friends to donate colorful, festive fabrics and heavy-duty ribbons for the apron sash to the club. Its members are still making the aprons. Donations are still needed.
“These aprons are amazingly efficient,” said Julie Bulger of VUMC Volunteer Services. “We have gotten great feedback from the women in the Vanderbilt Breast Center who have used them.”
The sewing club, which typically meets every third Monday between 10 a.m. and 2 p.m. at Vanderbilt Health One Hundred Oaks, makes between 10 and 15 aprons a month.
The club was recently honored by Hands on Nashville with the Civic Volunteer Group award.
“The supply cannot keep up with the demand,” Bulger said, noting that the sewing club also makes blankets, caps, seat belt pillows and mastectomy pillows.
– by Tom WIlemon
Jay Smith receives medal from Society of Urologic Surgery
The Society of Urologic Oncology (SUO) has recognized Joseph “Jay” Smith Jr., M.D., professor of Urologic Surgery, with the Huggins Medal, its highest honor, for his lifetime contributions to the progress in treatment for patients with genitourinary neoplasms, which are tumors or cancer of the reproductive organs and the urinary system.
The Huggins Medal is named after Charles B. Huggins, who was awarded the Nobel Prize for Physiology or Medicine in 1966 in recognition of his work on the hormonal treatment of prostate cancer.
It is the second major award for Smith from the SUO, having been awarded the SUO Medal in 2006.
“I remember as an intern choosing to go into urologic surgery and to pursue urologic oncology because I wanted to do what looked to be the most challenging operations. The Society of Urologic Oncology has been my most coveted peer group, so to be recognized in this manner is an enormous honor,” Smith said.
Smith, the William L. Bray Professor of Urology, was recently named the next editor of The Journal of Urology.
He performed Vanderbilt’s first robotic surgery in 2003 and has completed more than 7,000 prostatectomies since that time. With Smith, Vanderbilt University Medical Center has established itself as a leader in robotic surgery.
The Society of Urologic Oncology was created in 1984 to enable qualified members primarily interested in the care of patients with malignant genitourinary diseases to meet for the purpose of discussion, development and implementation of ideas to improve care.
– by Craig Boerner
VUMC to lead pilot program for precision medicine initiative
Vanderbilt University Medical Center (VUMC) will lead the Direct Volunteers Pilot Studies under the first grant to be awarded in the federal Precision Medicine Initiative Cohort Program.
White House officials and the director of the National Institutes of Health announced the grant and the selection of VUMC on Feb. 25.
The Precision Medicine Initiative Cohort Program’s objective is to build a broad and diverse national research cohort of 1 million or more U.S. volunteers whose participation will provide the platform for expanding approaches to precision medicine that will benefit the nation and medical science for decades to come.
The team of researchers involved with the Direct Volunteers Pilot Studies, whose objective is to create a prototype set of technologies and experiments that will inform the successful approach for such a large research cohort, also includes experts from Verily (formerly Google Life Sciences) as well as the University of Michigan and the Broad Institute of MIT and Harvard.
“We are excited to play an important role in developing the President’s Precision Medicine Initiative, as we work together to advance the understanding of how to enhance health and treat diseases. Our institutional investments in precision medicine, which began more than a decade ago, are bearing fruit, and we have an outstanding group of individuals in place to lead this effort,” said Jeff Balser, M.D., Ph.D., President and CEO of VUMC and dean of Vanderbilt University School of Medicine.
A pioneer in VUMC’s precision medicine efforts, Josh Denny, M.D., is the principal investigator.
“The Precision Medicine Initiative is a grand experiment on a scale that has never been tested before,” Denny said. “We’ll pilot how to authentically engage individuals to participate in the program and build the initial informatics and web infrastructures to support it.”
Precision medicine uses advanced approaches to data collection and analysis that rapidly assimilate unprecedented amounts of individuals’ personal health data, as well as behavioral and environmental data. This information, when combined with genetic and other molecular data, will provide a broad platform that can be used extensively for discoveries that will help advance the science of preventive care, as well as new treatments and potentially cures for diseases. The goal of precision medicine is to match individuals with treatments and preventive strategies that are most likely to work for them.
As part of the Direct Volunteers Pilot Studies, VUMC will create and optimize a prototype informational website that is engaging to a diverse array of potential volunteers.
– by John Howser
College of American Pathologists lauds Washington’s work
Mary (Kay) Washington, M.D., Ph.D., professor of Pathology, Microbiology and Immunology, has received the Lifetime Achievement Award from the College of American Pathologists (CAP).
The CAP Lifetime Achievement Award recognizes pathologists who have demonstrated a broad, positive impact on the pathology profession through contributions to the organization as well as helping improve the health care landscape for patients and laboratory medicine. CAP has more than 18,000 physician members and the organization is the leader in laboratory accreditation with more than 7,700 CAP-accredited laboratories in 50 countries.
Washington’s research focuses on diagnostic aspects of gastrointestinal and hepatic (liver) pathology, with special emphasis on Barrett’s esophagus, colorectal abnormalities, inflammatory bowel disease and the pathology of GI immune deficiencies. She has also been involved in evaluation of mouse models for neoplasia or growths in the intestines, as well as inflammatory bowel disease.
– by Dagny Stuart
IOM study calls for better access and uniformity with biomarker tests
Biomarker tests that help determine which patients may benefit from molecularly targeted therapies need better evidence and oversight to improve their effectiveness and availability, according to a study by the Institute of Medicine (IOM) of the National Academies of Sciences, Engineering, and Medicine.
The study authors said the tests are not being uniformly adopted into clinical practice because of a lack of common evidentiary standards necessary for regulatory, reimbursement and treatment decisions.
Harold L. (Hal) Moses, M.D., Ingram Professor of Cancer Research, chair of the Department of Cancer Biology and Director Emeritus of Vanderbilt-Ingram Cancer Center, served as chair of the national committee that produced the report.
“The timely development of biomarker tests and associated therapies is critical to realizing the full potential of precision medicine,” Moses said.
Biomarker tests for molecularly targeted therapies identify molecular variations specific to an individual patient. These tests can help determine which patients will or will not be helped by a targeted therapy and which therapies may actually be harmful.
Advances in research over the past 15 years have led to hundreds of molecularly targeted agents entering the drug development pipeline. Numerous biomarker tests have also been developed and marketed, but the committee found that progress has been hampered by regulatory and reimbursement uncertainties, clinical practice challenges and limitations in data collection and analysis.
The committee recommended that the Centers for Medicare and Medicaid Services work with private insurance companies to develop payment models that support ongoing data collection.
Yu Shyr, Ph.D., Harold L. Moses Professor Cancer Research, also served on the committee.
– by Dagny Stuart