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News from Around the Cancer Center

June 15, 2015

Program focuses on heart health of cancer patients

The Vanderbilt Cardio-Oncology program has fostered a special collaborative relationship combining the expertise of cardiologists and oncologists to understand the effects of cancer therapy on the heart. This type of collaboration is now helping to define the cardiovascular health of more than 14 million cancer survivors in the United States.

With nearly 3 million breast cancer survivors, and even more surviving prostate cancer in the United States, preventing or managing their heart disease has significant public health implications.

The incidence of heart disease has increased in cancer survivors in part as a direct result of cancer therapy itself and can manifest in various forms. This is especially true for breast cancer.

“Heart failure can be caused by breast cancer therapy, especially anthracyclines or trastuzumab. We have also begun to appreciate radiation therapy for breast cancer as a significant risk factor for heart attacks in breast cancer survivors,” said Javid Moslehi, M.D., who recently joined Vanderbilt Heart and Vascular Institute (VHVI) as the director of Cardio-Oncology.

“Early and aggressive efforts to reduce cardiac risk factors through lifestyle modification or with medical therapy represent the most important intervention to prevent [cardiovascular disease in cancer survivors],” Moslehi recently wrote in an editorial for the New England Journal of Medicine.

Moslehi, who came to Vanderbilt from Harvard Medical School in Boston, is collaborating with oncologist Debra Friedman, M.D., surgical urologist David Penson, M.D., interventional cardiologist David Slosky, M.D., and heart failure specialist Daniel Lenihan, M.D., to implement guidelines to prevent cardiovascular disease in cancer survivors.

At the heart of the guidelines is a simple concept that Moslehi refers to as ABCDE of cardiovascular disease prevention in cancer survivors: awareness, prophylactic aspirin; blood pressure control; cholesterol lowering, cigarette smoking cessation; diet, dose of chemotherapy, diabetes management; and exercise.

“These guidelines are going to be our platform for the Cardio-Oncology survivorship program here at Vanderbilt and is a simple way for cardiologists, oncologists and primary care physicians to address cardiovascular wellness in cancer survivors,” Moslehi said.

The cardiovascular health of cancer survivors will be a new focus of the National Comprehensive Cancer Network (NCCN), an alliance of 25 cancer centers in the United States whose goal is to advance the quality, effectiveness and efficiency of oncology care so that cancer patients can live better lives. Moslehi and Friedman represent Vanderbilt in the NCCN clinical practice guidelines in oncology survivorship.

The cardiovascular wellness guidelines in cancer survivors, which Moslehi is chairing, will be released later this year and will help define specifics of cardiovascular care for cancer survivors.

– by Kathy Whitney


Grant spurs lung cancer surgery research

Joe B. (Bill) Putnam Jr., M.D., Ingram Professor of Cancer Research and chair of the Department of Thoracic Surgery, has received a grant to investigate the most effective forms of surgery to treat lung cancer patients.

The award from the Agency for Healthcare Research and Quality (AHRQ), a division of the U.S. Department of Health and Human Services, will provide $954,000 in funding over four years.

While most patients are diagnosed when their disease is at an advanced stage, surgery provides cure rates between 77 and 92 percent when the disease is found early. However, there is a lack of information about what type of surgery is most effective, with the lowest complication rates, and the financial costs associated with different types of surgery.

The standard surgical approach to treating lung cancer involves a thoracotomy, a major invasive procedure that divides chest wall muscles and spreads the ribs to remove portions of the diseased lung.

However, surgeons are increasingly using the less invasive video assisted thoracic surgery (VATS), during which they make three or four small incisions and use a video camera to help find and remove the cancerous tissue.

“While we know that VATS has many post-surgical advantages in terms of pain and recovery time, it is not clear if this minimally invasive approach provides the same level of accuracy when it comes to identifying lymph nodes that may harbor cancerous cells,” said Putnam. “It is crucial that we identify metastatic lymph nodes to ensure that a patient has the best chance of surviving their cancer.”

To help determine the effectiveness of different surgical approaches, the AHRQ research led by Putnam and Fernandez will study information from the Society of Thoracic Surgeons General Thoracic Surgery Database, which includes patient-level clinical details not found in any other database.

– by Dagny Stuart


Cancer organizations call for regulation of e-cigarettes

Two leading cancer organizations are calling for regulation of e-cigarettes and other electronic nicotine delivery systems (ENDS).

The American Association for Cancer Research (AACR) and the American Society of Clinical Oncology (ASCO) issued the joint statement calling for greater oversight of the products and more research about their effects on the long-term health of users.

“As a physician-scientist who treats patients with cancer, I am concerned about the delayed time course that’s needed to assess the adverse impacts of ENDS use,” said Carlos L. Arteaga, M.D., professor of Medicine and Cancer Biology, director of the Center for Cancer Targeted Therapies and the Breast Cancer Program at Vanderbilt-Ingram Cancer Center and Donna S. Hall Professor of Breast Cancer. Arteaga is serving as president of the AACR this year.

“Therefore, although we call for additional research to determine with certainty the potential negative public health consequences of these products, particularly in youth, we cannot afford to wait to take prudent steps to stop those under 18 from using e-cigarettes.”

According to the cancer groups, tobacco use is responsible for 30 percent of all cancer deaths and is associated with increased risk for at least 18 types of cancer.

E-cigarettes and other ENDS, which are capable of delivering a nicotine solution in aerosolized form, have been promoted as potential tobacco cessation products and safer alternatives to cigarettes. However, e-cigarettes are currently unregulated and it is unclear if the chemicals used in the products are safe.

There is also no current scientific consensus on the effectiveness of ENDS as a smoking cessation tool.

– by Dagny Stuart


Penson to lead Department of Urologic Surgery

David Penson, M.D., the Paul V. Hamilton, M.D. and Virginia E. Howd Professor of Urologic Oncology, is now chair of Vanderbilt’s Department of Urologic Surgery.

Penson replaces Joseph Smith Jr., M.D., the William L. Bray Professor and former chair of the Department of Urologic Surgery, who will remain a valued member of VUMC’s faculty, maintain his clinical and surgical practice and continue to teach and mentor.

Vanderbilt is now one of the highest volume hospitals for urologic surgical procedures, with both its adult and Pediatric Urology divisions ranking among the top 10 programs in the country and one of only two departments nationally to own this distinction.

Penson received his undergraduate degree from the University of Pennsylvania, his medical degree from Boston University, received his residency training at UCLA, and fellowship training at Yale. He served as a member of the faculty at the University of Washington and USC before joining Vanderbilt in 2009.

– by Craig Boerner


Moses, Shyr named to Institute of Medicine cancer therapies panel

Two Vanderbilt-Ingram Cancer Center leaders have been named to a panel of the Institute of Medicine (IOM) to help shape national policies on the use of biomarkers for targeted cancer therapies.

Harold L. (Hal) Moses, M.D., Ingram Professor of Cancer Research and director emeritus of Vanderbilt-Ingram, will chair the IOM’s ad hoc committee, Policy Issues in the Clinical Development and Use of Biomarkers for Molecularly Targeted Therapies. Moses is a member of the IOM and founding chair of the group’s National Cancer Policy Forum.

Yu Shyr, Ph.D., director of the Vanderbilt Center for Quantitative Sciences and VANGARD (Vanderbilt Technologies for Advanced Genomics Analysis and Research Design), also will serve as a committee member.

New technologies have identified gene mutations in patient tumors as well as molecular biomarkers that signal key attributes of a patient’s disease. This information can be used to guide selection of therapies most likely to benefit a particular patient. The development of these new technologies and their use in clinical practice is a hallmark of precision medicine, which seeks to match the right therapy to the right patient at the right time.

“This is a critical time to examine these issues as the FDA is moving toward exerting more oversight and regulation of biomarker tests, and input from the broader scientific community should be helpful in assuring appropriate FDA oversight,” Moses said.

– by Dagny Stuart


New technique accelerates genome editing process

It sounds like a potato chip, but CRISPR is actually the acronym for a new genome editing technique that, by many accounts, is accelerating the study of genes and disease.

CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, was first described two years ago. It’s an adaptive immune response bacteria use to recognize and thwart “invasions” of viral and foreign DNA.

“It turns out that some species of bacteria have an ingenious system to protect themselves from viruses,” said Douglas Mortlock, Ph.D., scientific co-director of the Vanderbilt Transgenic Mouse/Embryonic Stem Cell Shared Resource.

“If viral DNA gets into their cell, they cut off a tiny bit of it and stick it in their own chromosome and later they can make an RNA copy of it … to scan any new invading DNA sequences,” he said. “If they match, it cuts the DNA.”

About a half dozen Vanderbilt labs are now using the technique, and more are ramping up to do it, he said.

A common way to study a mutation thought to cause human disease is to mutate the normal gene in an animal model, like the mouse, and see what happens.

Other gene mutation methods in mice can take 18 months and cost up to $20,000. “Now we can basically squirt this stuff into mouse embryos and three weeks later mice are born that have the mutation … at a cost of $3,000 or less,” Mortlock said. “It’s stunning.”

Vanderbilt researchers are using CRISPR to accelerate studies in cancer, type 2 diabetes, heart conditions, Huntington’s disease, Parkinson’s disease and restless legs syndrome.

“It is remarkably robust technology,” said Ian Macara, Ph.D., chair of the Department of Cell & Developmental Biology. “The first time we tried it, it worked … with amazing efficiency.”

– by Bill Snyder


Grant bolsters pancreatic cancer drug discovery efforts

The Lustgarten Foundation has awarded a $1.5 million Research Investigator Grant to Stephen Fesik, Ph.D., Orrin H. Ingram II Professor of Cancer Research and co-leader of the Signal Transduction and Chemical Biology Research Program, for research designed to discover new drugs for the treatment of pancreatic cancer.

Fesik is among 13 scientists nominated by their peers for significant achievements in the field of pancreatic cancer research who will receive a total of $19.5 million in research funding from the foundation.

This is Fesik’s second multi-year award from The Lustgarten Foundation in support of his research targeting K-Ras, a protein mutated in 90 percent of pancreatic cancer cases, as well as other forms of cancer.

The K-Ras protein controls many processes that are important for tumor cell growth, but it is a challenging protein to target and has been considered “undruggable.”

Fesik and his colleagues recently discovered small molecules that affect the function of K-Ras by binding to a regulatory protein (SOS) responsible for activating K-Ras. In preliminary testing, the molecules kill cancer cells by inhibiting Ras signaling.

“We do not yet understand why these small molecules function in this manner and the compounds are not currently potent enough for use as pharmaceutical agents. Nevertheless, they represent a promising starting point for discovering more potent compounds that inhibit K-Ras function and could be used to treat pancreatic and other Ras-driven types of cancer,” Fesik said.

The Lustgarten Foundation is the nation’s largest private funder of pancreatic cancer research aimed at detecting the disease in its earliest stage, identifying more effective treatment options and finding a cure.

– by Dagny Stuart