VICC News & Publications http://viccweb.gtm.mc.vanderbilt.edu/news Wed, 27 Aug 2014 16:28:11 +0000 en-US hourly 1 http://wordpress.org/?v=4.0 Study identifies genes tied to colon cancer http://viccweb.gtm.mc.vanderbilt.edu/news/2014/08/study-identifies-genes-tied-to-colon-cancer/ http://viccweb.gtm.mc.vanderbilt.edu/news/2014/08/study-identifies-genes-tied-to-colon-cancer/#comments Fri, 22 Aug 2014 15:13:53 +0000 http://viccweb.gtm.mc.vanderbilt.edu/news/?p=6977 by Dagny Stuart

Colorectal cancer is one of the leading causes of death among populations around the world. While diet, physical activity and other lifestyle factors can influence the risk of developing the disease, hereditary factors also play an important role.

Genetic factors identified to date explain only a small fraction of colorectal cancer (CRC), and most studies of hereditary risk have been conducted among people of European descent.

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Ben Zhang, MD, PhD, and Wei Zheng, MD, PhD ( tie ). Division of Epidemiology Vanderbilt University Medical Center. photo: Anne Rayner; VU

“It is important to conduct studies in different populations because the genetic structure may differ enough that some genetic risk variants identified in one population may not be related to the risk in other populations,” said Wei Zheng, M.D., Ph.D., Ingram Professor of Cancer Research and senior author of a new Vanderbilt-led study of East Asians published in Nature Genetics.

Zheng and his colleagues hypothesized that East Asians might be a particularly suitable population to study for genetic factors for CRC since they are less likely than people in the United States and European countries to receive CRC screening, which includes removal of polyps or other premalignant lesions that can lead to CRC.

Early detection and disease prevention may keep otherwise genetically susceptible individuals from being included in CRC population studies.

For the new investigation, researchers conducted a genome-wide association study of CRC among East Asians, including 14,963 cancer patients and 31,945 control subjects. The investigators identified six novel genetic loci that are associated with an increased risk of colorectal cancer among East Asians and suggestive evidence for three additional genetic loci.

“Genetic loci” refers to the location on a chromosome of genes and/or other DNA sequences. The investigators then collaborated with three research consortia conducted in European descendants and found that most of these newly identified risk variants also showed an association with CRC risk in European populations. Therefore, the results from the new studies are relevant to both Asian and European populations, Zheng noted.

Two of the genetic loci are linked to the genes TCF7L2 and TGFB1 that have established roles in the development of colorectal tumors. Four others are located in or near genes involved in cell signaling, growth, differentiation, motility and metastasis.

“Our findings provide additional insight into the genetics and biology of CRC,” said Ben Zhang, M.D., Ph.D., MPH, research assistant professor of Medicine and first author of the paper. “Newly identified regions may harbor potential targets for future novel cancer therapies, and genetic risk variants could be used for disease risk prediction.”

The new research was conducted as part of the Asia Colorectal Cancer Consortium, established in 2009, that includes population studies in China, Korea, Japan and Singapore. In a previous paper, also published in Nature Genetics, the group had reported the discovery of three genetic regions associated with CRC risk.

Vanderbilt investigators involved in the new research include Qiuyin Cai, M.D., Ph.D., Jirong Long, Ph.D., Jiajun Shi, Ph.D., Wanqing Wen, M.D., MPH, Gong Yang, M.D., MPH, Yanfeng Zhang, Ph.D., Chun Li, Ph.D., Bingshan Li, Ph.D., Yan Guo, Ph.D., and Xiao Ou Shu, M.D., Ph.D., MPH.

Funding for the study included grant support from the National Institutes of Health (NIH – R37CA070867, R01CA124558, R01CA148667, R01CA082729, UM1CA173640), and Ingram Professorship and Research Reward funds from the VU School of Medicine.

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Courage Unmasked supports cancer patients http://viccweb.gtm.mc.vanderbilt.edu/news/2014/08/courage-unmasked-supports-cancer-patients/ http://viccweb.gtm.mc.vanderbilt.edu/news/2014/08/courage-unmasked-supports-cancer-patients/#comments Wed, 06 Aug 2014 13:00:09 +0000 http://viccweb.gtm.mc.vanderbilt.edu/news/?p=6956 by Dagny Stuart

Charlie Haller had never smoked or used chewing tobacco and wasn’t a heavy drinker, so the 41-year-old Lyles, Tennessee, man wasn’t thinking about cancer when a mass developed on the side of his neck.

Barbara Murphy, M.D., with patient Charlie Haller, who is receiving treatment for head and neck cancer at Vanderbilt-Ingram Cancer Center. (photo by Joe Howell)

Barbara Murphy, M.D., with patient Charlie Haller, who is receiving treatment for head and neck cancer at Vanderbilt-Ingram Cancer Center. (photo by Joe Howell)

His primary care physician, however, immediately referred him to a specialist and a biopsy revealed a form of head and neck cancer that had already invaded soft tissue in Haller’s nasal passage and the base of his tongue.

It was a diagnosis he wasn’t expecting.

“It just goes to show it does strike everybody,” said Haller.

He has already started a chemotherapy regimen at Vanderbilt-Ingram Cancer Center (VICC), and the next step will be 35 sessions of radiation therapy.

Like every patient undergoing radiation to the head and neck region, Haller was fitted for a personalized mask, a plastic mesh contraption that must be heated and pulled tightly over the patient’s face to capture the contours of the head and facial features.

The fitting for the mold takes about 15 minutes, then the mask is cured until it hardens.

The mask is used during each radiation treatment to ensure that the radiation beam is targeting the cancer while sparing healthy tissue nearby.

Personalized radiation therapy masks are part of a special cancer fundraising project called Courage Unmasked. (photo by john Russell)

Personalized radiation therapy masks are part of a special cancer fundraising project called Courage Unmasked. (photo by john Russell)

Haller immediately saw the mask as a tool, perhaps because he uses tools to design automotive repairs in his job as a technical specialist at Nissan U.S.A., but he understands how intimidating the masks look.

“You would think Medieval, like a swordsman and coat of armor and a helmet. I would see where some folks, it would make them nervous,” Haller said.

His medical oncologist, Barbara Murphy, M.D., professor of Medicine and director of Head and Neck Oncology at VICC, said being confined in the mask is traumatic for many patients.

“It molds to the face and patients are bolted to a table. They are by themselves and run through a machine, and this is done up to 30 times or more for treatment,” Murphy said.

Even with a cure, the intensive treatments in such a delicate area can cause severe side effects that often affect speech, swallowing, taste, smell and nutrition.

“In addition to physical side effects, patients may be profoundly affected emotionally and psychologically. Thus the mask becomes highly symbolic for patients,” said Murphy.

More than 60 patients donated their masks for a fundraising project called Courage Unmasked. Each mask is given to a local artist, who crafts a unique design and transforms the mask into a piece of art.

Some of the artists confer with the patient who donated the mask and incorporate details from the patient’s experience into the final design concept.

The first few decorated masks will be unveiled Thursday, Aug. 7, at Miller Piano, with a full display later at Gallery 202, both in Franklin, Tennessee.

The stylized masks will be auctioned during a special Courage Unmasked fundraising event Sept. 27, at OZ, a Nashville arts and events venue. Eventually, the masks will be displayed at the Sarratt Gallery at Vanderbilt.

Funds will benefit the VICC Caring Hearts Fund and will be used for financial support for head and neck cancer patients.

The Nashville shows represent the first time a Courage Unmasked event has been held outside of Washington, D.C.

“The marriage of the cold, scientific device which is a necessary evil to achieve cure with the artists’ interpretation of the experience will be fascinating to see,” said Murphy.

Haller said those who donate are showing a commitment to helping future patients. It’s the same reason he signed up to participate in a clinical research trial.

“This is a way I could help someone else. It’s all voluntary…we need to help other folks, that’s what makes us who we are,” Haller said.

For more information about Courage Unmasked, visit www.courageunmaskedtn.org

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New target for breast cancer therapy http://viccweb.gtm.mc.vanderbilt.edu/news/2014/08/new-target-for-breast-cancer-therapy/ http://viccweb.gtm.mc.vanderbilt.edu/news/2014/08/new-target-for-breast-cancer-therapy/#comments Mon, 04 Aug 2014 13:00:13 +0000 http://viccweb.gtm.mc.vanderbilt.edu/news/?p=6953 by Leigh MacMillan

The protein MTBP is important for growth and survival of triple negative breast cancer (TNBC) – a clinically aggressive subtype of breast cancer that is commonly resistant to targeted therapeutics – Vanderbilt investigators have discovered.

Using data from The Cancer Genome Atlas, Christine Eischen, Ph.D., MSTP student Brian Grieb, Ph.D., and colleagues found that MTBP is overexpressed in breast cancer, with the highest levels in TNBC. They demonstrated that MTBP levels were elevated in a panel of human TNBC cell lines, and that reducing MTBP levels caused cell death and reduced tumor growth in vitro and in vivo in animal models, including in established tumors.

The researchers also found that MTBP is a novel regulator of MYC, an oncogenic factor that is overexpressed in 70 percent of human cancers. They showed that MTBP associates with MYC and increases MYC-mediated cell growth and tumor development.

The findings, published in two papers in Molecular Cancer Research and Cancer Research, position MTBP as a novel therapeutic target for human cancer, including TNBC.

This research was supported by grants from the National Institutes of Health (AG039164, GM007347, CA148950, CA098131, TR000445, CA068485, CA119925).

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Komen breast cancer research grants http://viccweb.gtm.mc.vanderbilt.edu/news/2014/08/komen-breast-cancer-research-grants/ http://viccweb.gtm.mc.vanderbilt.edu/news/2014/08/komen-breast-cancer-research-grants/#comments Fri, 01 Aug 2014 13:00:04 +0000 http://viccweb.gtm.mc.vanderbilt.edu/news/?p=6966 by Dagny Stuart

Two Vanderbilt-Ingram Cancer Center investigators have received multi-year breast cancer research grants from the Susan G. Komen for the Cure Breast Cancer Foundation.

Carlos Arteaga, M.D., left, with Justin Balko, Ph.D., Pharm.D., one of two investigators who recently received support from the Susan G. Komen for the Cure Breast Cancer Foundation. (photo by Susan Urmy)

Carlos Arteaga, M.D., left, with Justin Balko, Ph.D., Pharm.D., one of two investigators who recently received support from the Susan G. Komen for the Cure Breast Cancer Foundation. (photo by Susan Urmy)

Justin Balko, Ph.D., Pharm.D., research assistant professor of Medicine, won support for his research project which will use molecular profiling to prioritize adjuvant targeted therapy for triple negative breast cancer (TNBC) patients. TNBC is one of the most aggressive and hard-to-treat forms of breast cancer.

Joan Garrett, Ph.D., research instructor in Medicine, will investigate how breast cancers optimize HER3 signaling to drive therapeutic resistance. HER3 is a tyrosine kinase receptor and breast cancers with alterations in HER3 are linked to worse survival for patients.

The Komen Career Catalyst Research (CCR) awards are three-year grants totaling $450,000 for each investigator. The CCR grants provide opportunities for young scientists to progress toward research independence.

Both investigators work in the laboratory of Carlos L. Arteaga, M.D., Donna S. Hall Professor of Breast Cancer, associate director for Clinical Research at VICC, director of the Center for Cancer Targeted Therapies (CCTT) and director of the Breast Cancer Program.

Arteaga is recognized as a world-renowned breast cancer investigator who is also providing training and guidance for the next generation of cancer researchers.

Garrett recently accepted a new post out of state. Arteaga said serving as a scientific and career mentor to young investigators is one of his priorities.

“In addition to providing leading-edge therapies for breast cancer patients, our Breast Cancer Program offers a superior training opportunity, with intensive mentorship, for talented young scientists,” said Arteaga.

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Study on breast cancer in East Asian women http://viccweb.gtm.mc.vanderbilt.edu/news/2014/07/study-on-breast-cancer-in-east-asian-women/ http://viccweb.gtm.mc.vanderbilt.edu/news/2014/07/study-on-breast-cancer-in-east-asian-women/#comments Tue, 29 Jul 2014 13:00:54 +0000 http://viccweb.gtm.mc.vanderbilt.edu/news/?p=6945 by Dagny Stuart

A new study in East Asian women has identified three genetic changes linked to an increased risk of breast cancer. The

Qiuyin Cai, M.D., Ph.D., and colleagues have identified three genetic changes linked to breast cancer risk in East Asian women. (photo by John Russell)

Qiuyin Cai, M.D., Ph.D., and colleagues have identified three genetic changes linked to breast cancer risk in East Asian women. (photo by John Russell)

research, led by Vanderbilt University investigators, was published online this week in Nature Genetics.

While breast cancer is one of the most common malignancies among women worldwide, most studies of the genetic risk factors for the disease have focused on women of European ancestry.

Given the differences in genetic heritage and environmental exposures between East Asian women and those of European ancestry, the investigators decided to conduct a study in East Asians to search for genetic changes that are linked to breast cancer development. The current study was conducted as part of the Asia Breast Cancer Consortium led by Wei Zheng, M.D., Ph.D., MPH, Ingram Professor of Cancer Research at Vanderbilt.

First author Qiuyin Cai, M.D., Ph.D., associate professor of Medicine, and colleagues performed a genome-wide association study of 22,780 women with breast cancer, and 24,181 control subjects who were recruited in 14 studies in Asian countries, including China, Japan, Korea, Malaysia and Singapore.

DNA for the gene assays was obtained through blood samples or buccal cells from mouthwash.

“We found DNA sequence changes in two genes, PRC1 and ZC3H11A, and a change near the ARRDC3 gene were associated with breast cancer risk and we identified a possible association with a fourth gene locus,” said Cai.

“Two of those sequence changes are in parts of the genome that regulate the expression of nearby genes.”

ARRDC3 and PRC1 genes were previously linked to breast cancer growth and poor survival in breast cancer patients, respectively. The role of ZC3H11A in breast cancer is unknown.

These DNA sequence changes may affect the regulation of cell growth, tumor cell migration and invasion, or metastasis.

These results were also replicated in a large consortium, including 16,003 breast cancer cases and 41,335 control subjects of European ancestry, as reported by the authors.

The risk of breast cancer conferred by each of these new genetic markers is relatively small.

However, these new markers could be combined in the future with other breast cancer predictors, including genetic markers identified previously, to identify potentially high-risk women for screening and other prevention programs.

Results from this study provide additional insights into the genetics and biology of breast cancer. Based on these findings, the authors say further studies of possible mechanisms through which these loci and genes are involved in breast cancer development are warranted.

Other Vanderbilt investigators involved in the study include Ben Zhang, M.D., Ph.D., MPH, Jiajun Shi, Ph.D., Jirong Long, Ph.D., Wanqing Wen, M.D., MPH, Ryan Delahanty, Ph.D., Yanfeng Zhang, Ph.D., Bingshan Li, Ph.D., Chun Li, Ph.D., Xiao Ou Shu, M.D., Ph.D., MPH, and Wei Zheng, M.D., Ph.D., MPH.

The Vanderbilt-led research was primarily funded by the U.S. National Institutes of Health (R01CA124558, R01CA148667, R37CA070867, R01CA118229, R01CA092585, R01CA064277, R01CA122756, and R01CA137013); Department of Defense Idea Awards (BC011118 and BC050791); and Vanderbilt-Ingram Cancer Center, (Ingram Professorship).

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Colon cancer’s protein signatures identified http://viccweb.gtm.mc.vanderbilt.edu/news/2014/07/colon-cancers-protein-signatures-identified/ http://viccweb.gtm.mc.vanderbilt.edu/news/2014/07/colon-cancers-protein-signatures-identified/#comments Fri, 25 Jul 2014 20:00:55 +0000 http://viccweb.gtm.mc.vanderbilt.edu/news/?p=6939 by Bill Snyder

A Vanderbilt University-led research team has identified protein “signatures” of genetic mutations that drive colorectal cancer, the nation’s second leading cause of cancer deaths after lung cancer.

Dan Liebler, Ph.D., and colleagues identified protein “signatures” of genetic mutations that drive colorectal cancer, the nation’s second leading cause of cancer deaths after lung cancer. (photo by Susan Urmy)

Dan Liebler, Ph.D., and colleagues identified protein “signatures” of genetic mutations that drive colorectal cancer, the nation’s second leading cause of cancer deaths after lung cancer. (photo by Susan Urmy)

The technological tour de force, described as the first integrated “proteogenomic” characterization of human cancer, was reported online this week by the journal Nature. It “will enable new advances” in diagnosing and treating the disease, the researchers concluded.

“It’s a first-of-its-kind paper. I think it’s a very important advance in the field,” said senior author Daniel Liebler, Ph.D., Ingram Professor of Cancer Research and director of the Jim Ayers Institute for Precancer Detection and Diagnosis at the Vanderbilt-Ingram Cancer Center.

The research team, representing Vanderbilt and six other institutions, is part of the Clinical Proteomic Tumor Analysis Consortium (CPTAC), sponsored by the National Cancer Institute of the National Institutes of Health.

Proteomics is the study of proteins. While many genetic mutations associated with cancer have been identified, it has been more difficult to analyze the structure and function of proteins that actually do cancer’s “work.” Until now.

The researchers used advanced mass spectrometry techniques to gather proteomic data on 95 human colorectal tumor samples characterized previously by The Cancer Genome Atlas, a federally funded project to identify genetic abnormalities in cancer.

Data analysis was led by first author Bing Zhang, Ph.D., associate professor of Biomedical Informatics. ”Integrating the proteomics data with the vast amount of pre-existing genomic data is a daunting task,” Zhang said, “however, it is also the key to turn the data into novel insights.”

Jim Ayers, center, greets members of the research team during an Ayers Institute board meeting in April. From left are Qi Liu, Ph.D., Zhiao Shi, Ph.D., and the paper's first author, Bing Zhang, Ph.D. Janet Ayers is at far right. (photo by Joe Howell)

Jim Ayers, center, greets members of the research team during an Ayers Institute board meeting in April. From left are Qi Liu, Ph.D., Zhiao Shi, Ph.D., and the paper’s first author, Bing Zhang, Ph.D. Janet Ayers is at far right. (photo by Joe Howell)

It is a basic biological principle that DNA — the genetic code — is “transcribed” into messenger RNA, then “translated” into proteins. Yet the researchers found that abnormalities in the genes or even the RNA of the samples did not necessarily “translate” into abnormal proteins.

Similarly, some sections of chromosomes that were “amplified” in the tumor samples did not result in amplified or increased protein levels.

Those that did, however, produced “striking effects,” suggesting that proteomics might help identify and prioritize the most “impactful” genetic abnormalities that could be targets for new diagnostic tests or drug treatments, Liebler said.

The researchers also identified five subtypes of colon cancer based on their protein content, one of which was associated with poor outcomes. Proteomics thus may help identify patients who would benefit most from chemotherapy after surgery.

“Our discovery of proteomic subtypes opens the door to protein-based diagnostics that could potentially identify the bad cancers that need the aggressive therapy,” Liebler said. “That’s what we’re really hot on going forward.”

Liebler said that the support of the Ayers Institute, established in 2005 with a $10 million gift from Jim Ayers, chairman of FirstBank in Lexington, Tenn., and his wife Janet Ayers, was critical for building the infrastructure for conducting the research.

“Without the Ayers Institute, we wouldn’t have been in a position to even apply for the CPTAC program, to be a part of this at all,” he said.

“This is exciting news that appears to have tremendous implications for cancer diagnosis and treatment,” Janet Ayers said. “Jim and I extend our congratulations to Dr. Liebler and the team working with the Jim Ayers Institute for Precancer Detection and Diagnosis at the Vanderbilt-Ingram Cancer Center.

“These are the kinds of discoveries we hoped for when the institute was launched just a few years ago,” she said. “To start seeing results like this so quickly is extremely rewarding.”

Vanderbilt co-authors from the departments of Biochemistry, Biomedical Informatics, Computer Science and Surgery were Jing Wang, Ph.D., Xiaojing Wang, Ph.D., Jing Zhu, Ph.D., Qi Liu, Ph.D., Zhiao Shi, Ph.D., Matthew Chambers, Lisa Zimmerman, Ph.D., Kent Shaddox, David Tabb, Ph.D., Robert Coffey Jr., M.D., and Robert J.C. Slebos, Ph.D.

Others were from the Pacific Northwest National Laboratory in Richland, Washington, Washington University School of Medicine in St. Louis, Seattle’s Fred Hutchinson Cancer Research Center, New York’s Icahn School of Medicine at Mount Sinai, the National Cancer Institute and the Broad Institute of MIT and Harvard.

The study was supported by NIH grants CA159988, CA160035, CA160034, CA095103, CA068485 and GM088822.

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Abramson lands breast cancer research award http://viccweb.gtm.mc.vanderbilt.edu/news/2014/07/abramson-lands-breast-cancer-research-award/ http://viccweb.gtm.mc.vanderbilt.edu/news/2014/07/abramson-lands-breast-cancer-research-award/#comments Wed, 23 Jul 2014 13:00:56 +0000 http://viccweb.gtm.mc.vanderbilt.edu/news/?p=6933 by Dagny Stuart

 

Vandana Abramson, M.D.

Vandana Abramson, M.D.

 

Vandana Abramson, M.D., assistant professor of Medicine and a breast cancer specialist at Vanderbilt-Ingram Cancer Center, has received the Advanced Clinical Research Award in Breast Cancer from the Conquer Cancer Foundation (CCF).

The CCF grants and awards support cancer research done by physician-scientists at every stage of their careers.

Abramson’s Advanced Clinical Research Award (ACRA) in Breast Cancer was announced during the 50th Annual Meeting of ASCO, held recently in Chicago. Only one ACRA grant is awarded each year.

“I am thrilled and honored to receive this important grant award from the Conquer Cancer Foundation of the American Society of Clinical Oncology,” said Abramson. “This crucial funding will help support my research to improve therapies for breast cancer patients.”

Abramson will receive the ACRA in Breast Cancer grant totaling $450,000 over three years for research that includes two complementary clinical trials that use recent advances in the molecular understanding of triple negative breast cancer (TNBC).

The trials highlight novel, molecularly targeted treatments for recently defined subtypes of TNBC, which is one of the most aggressive forms of breast cancer.

This year’s ACRA award is also supported by funding from the Breast Cancer Research Foundation.

The CCF was created by cancer physicians of the American Society of Clinical Oncology (ASCO) to seek dramatic advances in the prevention, treatment and cure for all types of cancer.

Abramson received her Bachelor of Arts in English and Molecular & Cell Biology from the University of California, Berkeley, and earned her M.D. from the University of Chicago. She completed a residency in Internal Medicine at Brigham and Women’s Hospital in Boston and Hematology/Oncology training at the University of Pennsylvania, in Philadelphia. She joined the Vanderbilt faculty in 2009.

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Research bolstered by lung cancer foundation http://viccweb.gtm.mc.vanderbilt.edu/news/2014/07/research-bolstered-by-lung-cancer-foundation/ http://viccweb.gtm.mc.vanderbilt.edu/news/2014/07/research-bolstered-by-lung-cancer-foundation/#comments Mon, 21 Jul 2014 13:00:02 +0000 http://viccweb.gtm.mc.vanderbilt.edu/news/?p=6930 by Dagny Stuart

Christine Lovly, M.D., Ph.D.

Christine Lovly, M.D., Ph.D.

The LUNGevity Foundation has awarded a 2014 Career Development Award for Translational Research to Christine Lovly, M.D., Ph.D., assistant professor of Medicine and Cancer Biology.

Lovly is one of three recipients of the annual grants, which provide $300,000 over three years for lung cancer research.

“This is a wonderful award and I am so pleased and honored that the LUNGevity Foundation has decided to support this important research,” said Lovly.

The LUNGevity Foundation is a nonprofit organization dedicated to accelerating research into early detection and more effective treatments for lung cancer, in addition to providing community support and education for patients and families.

The Foundation’s Scientific Advisory Board is led by Pierre Massion, M.D., Ingram Professor of Cancer Research and director of the Thoracic Program at Vanderbilt-Ingram Cancer Center.
 The LUNGevity Career Development Award will help fund Lovly’s project to study why drugs that target a specific gene fusion in lung cancer eventually stop working.

Molecular alterations in the ALK gene are detected in a small percentage of patients with lung cancer. Drugs which inhibit or block the activity of ALK have demonstrated remarkable clinical results in patients with ALK+ lung cancer.

Unfortunately, despite these results, virtually all of the patients eventually develop resistance to the therapy.

The goal of Lovly’s research is to develop novel, rationally selected therapeutic strategies to delay and/or overcome acquired resistance to ALK inhibitor drugs.

Using a combination of experimental approaches, including cell culture models, biochemical assays and a study of patient tumor samples prior to and at the time of acquired resistance to ALK tyrosine kinase inhibitor therapy, she will study how ALK transmits signals to promote cancer growth and how these signals become altered in the context of acquired resistance. This work will identify novel targets that can be blocked, in combination with ALK inhibitors, to promote enhanced anti-tumor responses.

The results of these studies are expected not only to provide additional insight into ALK+ lung cancer, but will also extend to many other cancers that also harbor ALK molecular alterations.

In addition to her laboratory work, Lovly is co-editor of My Cancer Genome, a Vanderbilt-powered freely available online resource that provides up-to-date information about tumor gene mutations and implications for targeted therapies.

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Breast tissue protein may promote cancer http://viccweb.gtm.mc.vanderbilt.edu/news/2014/07/breast-tissue-protein-may-promote-cancer/ http://viccweb.gtm.mc.vanderbilt.edu/news/2014/07/breast-tissue-protein-may-promote-cancer/#comments Fri, 18 Jul 2014 12:00:16 +0000 http://viccweb.gtm.mc.vanderbilt.edu/news/?p=6924 by Bill Snyder

Ian Macara, Ph.D., right, Yongliang Huo, Ph.D., and colleagues are studying a protein that may play a role in breast cancer.

Ian Macara, Ph.D., right, Yongliang Huo, Ph.D., and colleagues are studying a protein that may play a role in breast cancer.

A protein essential for growth of normal breast tissue also may play a role in breast cancer, Vanderbilt University researchers have found.

Reporting recently in Nature Cell Biology, Yongliang Huo, Ph.D., and Ian Macara, Ph.D., for the first time describe the function of a protein called Par3L, which is expressed by a gene Macara and colleagues discovered at the University of Virginia in 2002.

Par3L is very similar to another protein, Par3, which functions as a polarity protein. That means it helps determine the “top-bottom” orientation of cells, including the adult stem cells that give rise to new epithelial tissues throughout the body, including the breast.

Epithelial cells line the ducts that produce milk in the breast, and pump it to the nipples. Normal growth of breast tissue occurs during each menstrual cycle, and during pregnancy and lactation. However, the biological role of Par3L itself was completely unknown.

Macara, who came to Vanderbilt in 2012 to chair the Department of Cell and Developmental Biology, and Huo, a postdoctoral fellow in his lab, found that Par3L is present specifically in mammary stem cells, and at the growing tips of mammary ducts.

If the gene for Par3L is deleted or “knocked down,” mammary stem cells in the mouse die, and mammary tissue doesn’t grow.

Huo discovered the mechanism: Normally Par3L “puts the brakes” on another polarity protein called LKB1, which suppresses mammary tissue growth. LKB1 is an important regulator of growth — loss of LKB1 can cause cancer in several organs, including the breast, but too much LKB1 can kill cells.

Without Par3L to tamp down the activity of this protein, LKB1becomes over-active and stem cells quickly die. If, on the other hand, Par3L is overexpressed, it acts as a “tumor promoter” by shutting down LKB1 and promoting uncontrolled growth, not only in the breast but in other tissues.

“We really need to know more about what this protein does and how it works,” said Macara, a Louise B. McGavock Professor in the department.

Eighty percent of all human cancers and all breast cancers arise from epithelial tissues. “There’s a lot of evidence that stem cells are the cells of origin of breast cancer,” he said, but “there’s still much that we don’t understand about the mammary stem cells themselves.

“How do they produce all the different cells in the ducts of the breast? How do they know when to grow and when to stop growing?

“We’re hoping to investigate this more rigorously in the future, and really begin to understand how polarity proteins contribute to the development of breast tissue, and to the defects that lead to breast cancer,” Macara said.

The study was supported by NIH grant GM070902 and a Department of Defense postdoctoral fellowship grant.

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Pietenpol joins IOM Cancer Policy Forum http://viccweb.gtm.mc.vanderbilt.edu/news/2014/07/pietenpol-joins-iom%e2%80%88cancer-policy-forum/ http://viccweb.gtm.mc.vanderbilt.edu/news/2014/07/pietenpol-joins-iom%e2%80%88cancer-policy-forum/#comments Thu, 10 Jul 2014 21:33:09 +0000 http://viccweb.gtm.mc.vanderbilt.edu/news/?p=6918 by Dagny Stuart

Jennifer Pietenpol, Ph.D., B.F. Byrd Jr. Professor of Oncology and director of Vanderbilt-Ingram Cancer Center, has been named an at-large member of the National Cancer Policy Forum, an advisory group of the Institute of Medicine (IOM) of the National Academies.

Jennifer Pietenpol, Ph.D.

Jennifer Pietenpol, Ph.D.

The IOM established the forum to serve as a trusted venue for national leaders from multiple sectors to work cooperatively to address high-priority policy issues in the nation’s effort to combat cancer.

Pietenpol is serving a three-year term.

“It is a wonderful privilege and honor to be invited to participate as a member of this forum,” said Pietenpol, who also heads a VICC research laboratory focusing on the molecular underpinnings of cancer. “We are at a crucial juncture in cancer research as we elucidate genetic changes that contribute to cancer, and we will need a focused and coordinated effort to use this information for the development of improved prevention strategies and therapies for patients worldwide.”

Members of the National Cancer Policy Forum work together to identify emerging high-priority policy issues in science, clinical medicine and public health relevant to the prevention and treatment of cancer.

Participants include clinicians, patients, researchers, professional and advocacy organizations, pharmaceutical manufacturers and policymakers. The forum enables all members to be full participants in discussing critical policy issues and examining strategies for improvement, and the group produces publicly available reports.

During the most recent meeting, members examined the issue of escalating treatment costs, as well as shortages of some cancer drugs and the impact of these issues on cancer patients and their families.

In June 2008, Pietenpol was appointed to a six-year term on the 12-member National Cancer Advisory Board of the NIH’s National Cancer Institute. She is a member of the Susan G. Komen for the Cure Scientific Advisory Committee and has been on the board of directors of the American Association for Cancer Research.

Pietenpol has served as associate editor or on the editorial board for numerous biomedical research journals. She has authored or co-authored more than 110 articles published in peer-reviewed scientific publications and is an elected fellow of the American Association for the Advancement of Science.

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