Jefferson Post-Doc Receives National Cancer Center Fellowship

Dr. Edward Hartsough

Dr. Edward Hartsough

Edward Hartsough, Ph.D. received a post-doctoral fellowship from the National Cancer Center Organization ( http://www.nationalcancercenter.org/ ).  The fellowship grant is entitled “Next-Generation RAF Inhibitors in V600E BRAF Melanoma.”  Dr. Hartsough works in Dr. Andrew Aplin’s lab at the Kimmel Cancer Center.

The National Cancer Center was founded by Dr. J. Ernest Ayre in 1953 as a non-profit organization committed to research and education about cancer. Melanoma is the deadliest form of skin cancer and its incidence is on the rise. BRAF mutations are found in half of melanomas and the funded work will study new mutant BRAF targeting agents in preclinical models.




Team Jefferson at 2013 Get Your Rear in Gear Race

Mika Harding, Richard Pestell, and Ruslan Banatskiy at this year's GYRIG race

Supporters of the Kimmel Cancer Center joined “Team Jefferson” for this year’s Get Your Rear in Gear 5K and 10K runs, 2 mile walk or a kids’ fun run.

Proceeds support cutting edge research in colorectal cancer and compassionate care.

Maria Grasso, founder and organizer of GYRIG Philadelphia, presented a check to Jefferson from last year’s event proceeds in the amount of $50,000 a week before the race.

A resident of Mount Laurel, N.J., Grasso lost her own father and grandfather to colon cancer.   Inspired by a desire to fight the diseases that claimed her loved ones, Grasso has grown the event from a few hundred participants to more than 4,000 as she approached the fifth year.

This annual race event is part of awareness and fund-raising efforts during March, National Colorectal Cancer Awareness Month.



Jefferson Graduate Student Receives 2013 Joanna M. Nicolay Melanoma Foundation Award

JMNMF President Greg Safko and Jefferson's Curtis Kugel

Curtis Kugel, a Thomas Jefferson University graduate student in the Department of Cancer Biology, was one of 10 students from leading cancer centers across the U.S. to receive a $10,000 “Research Scholar Award” (RSA) from the Joanna M. Nicolay Melanoma Foundation (JMNMF) for his exceptional research work.

JMNMF Chair, Regina Shannon Bodnar, and Board/RSA Committee member, Esther Hoffberg.  and JMNMF President Greg Safko, presented the award to Mr. Kugel at the Kimmel Cancer Center’s Bluemle Life Sciences Building on March 20.

Kugel was also accompanied by Dr. Richard Pestell, Director of the Kimmel Cancer Center, and Andrew Aplin, Ph.D., an Associate Professor in the Department of Cancer Biology.

Kugel’s research focuses on targeting receptor tyrosine kinases in an attempt to prevent resistance to RAF inhibitors in melanoma and improve the efficacy of those inhibitors.

“I am very excited to have been chosen to receive this award from the JMNMF for my work on melanoma research,” said Kugel. “With applicants working alongside some of the leading melanoma researchers and applying from some of the country’s top cancer centers, receiving this award is truly an honor.”

The JMNMF is a nonprofit public charity founded in January 2004 to foster melanoma education, advocacy and research. In just eight years, the Foundation has grown dramatically to become an influential voice in the melanoma community and is now established as a national, and international, “voice for melanoma prevention, detection, care and cure.”

The nationally competitive grants increased by nearly 11 percent in 2013 (following a 30 percent funding increase in 2011) to significantly enhance the potential for advancements in the melanoma cancer field and encourage a larger number of students to choose melanoma research as their professional career path.

The 2013 RSA applicant pool and cancer research centers represented grew to include 44 of the country’s most promising young melanoma researchers, and 28 prominent National Cancer Institute (NCI)-Designated Cancer Centers.

As first in the U.S. to fund graduate student melanoma researchers, the JMNMF program is celebrating the program’s seventh anniversary.

According to Regina Shannon Bodnar, “Our Foundation’s ‘Research Scholar Awards’ are invaluable at the grassroots level, to specifically grow interest in melanoma research, at leading cancer research centers nationwide.  If we can attract the brightest young minds, that are considering or are already within the nation’s cancer research pipelines, to pursue a career in melanoma research – we’re that much closer to better understanding the disease, identifying the means for effective treatments and, most importantly, finding a cure for this deadly and increasingly prevalent disease.”

For more information about JMNMF, please visit: http://www.melanomaresource.org/



Remembering ASCO Founding Member Dr. Jane Cooke Wright

Standing left to right - Dr. LaSalle D. Leffall, Jr.; Dr. Robert L. Comis; Dr. Stanley R. Hamilton; Dr. Randall C. Morgan; Dr. Al B. Benson, III; Dr. Edith P. Mitchell. Seated – Dr. Jane Cooke Wright.

In February, the American Society of Clinical Oncology (ASCO) announced the passing of Jane Cooke Wright, M.D., a true pioneer, mentor, and renowned researcher. Dr. Wright was one of seven founding members of ASCO – the only woman among the founders – and the Society’s first Secretary/Treasurer. She died on Tuesday, February 19 at the age of 93.

Pictured above, Dr. Edith Mitchell, a Clinical Professor of Medicine and Medical Oncology in the Department of Medical Oncology at Jefferson Medical College of Thomas Jefferson University, and Director of the Center to Eliminate Cancer Disparities, is joined by other ASCO members and physicians, with Dr. Wright seated.



2nd Annual Spring Fling

Please join us for our 2nd Annual Spring Fling benefiting the Helping Hand Fund for cancer patients and caregivers.

Save The Date Announcement

April 12, 2013
8:00 PM to MIDNIGHT
The Waterfall Room
2015 S. Water Street, Philadelphia, PA 19148

Tickets $50.00
Includes buffet dinner, top-shelf open bar,
dancing, raffles, 50/50 and door prizes

Contact Mia Burgis or Nicole Ferroni
mia.burgis@jefferson.edu or nicole.riverso@yahoo.com



Massimo Cristofanilli, M.D., Appointed Director of the Jefferson Breast Care Center

Massimo Cristofanilli, M.D.

Massimo Cristofanilli, M.D., FACP, an internationally renowned breast cancer researcher and clinician, has been appointed Director of the Jefferson Breast Care Center at the Kimmel Cancer Center (KCC) and Thomas Jefferson University and Hospitals.

With more than 25 years of clinical, basic science and educational experience, Dr. Cristofanilli will also serve as Deputy Director of Translational Research at the KCC.

Prior to joining Jefferson, Dr. Cristofanilli served as chairman of the department of medical oncology at Fox Chase Cancer Center and head of the center’s Inflammatory Breast Cancer Clinic. Before that, he founded and served as Executive Director of the Morgan Welch Inflammatory Breast Cancer Program and Clinic at The University of Texas M.D. Anderson Cancer Center in Houston.

Dr. Cristofanilli is a widely-recognized leader in the translational research and treatment of inflammatory breast cancer (IBC), the rare and aggressive form of breast cancer in which cancer cells block lymph vessels in the skin of the breast. Moreover, he has recognized expertise in the development of novel diagnostic and prognostic markers in primary and metastatic breast cancer (MBC).

“Dr. Cristofanilli is a proven leader whose translational research expertise will fit in perfectly with the overall mission of the KCC to link our already excellent basic science in breast cancer with more patient-directed therapies in a time-efficient manner,” said Richard G. Pestell, M.D., Ph.D., Director of the KCC and Chair of the Department of Cancer Biology and Vice President for Oncology Services at Jefferson. “We look forward to tackling some of the most innovative questions in breast cancer precision oncomedicine with cutting edge research and the latest clinical trials.”

Dr. Cristofanilli’s research aims to improve personalized medicine for breast cancer patients, focusing on molecular targeted agents, biomarkers and gene therapies, and bridging the gap between the bench and bedside in a more practical and smarter way. A forte of Dr. Cristofanilli is his team-based and multidisciplinary approach to medicine.

His 2004 study published in The New England Journal of Medicine on circulating tumor cells (CTCs)—found to be a predictor of progression-free survival and overall survival in MBC patients—sparked a slew of subsequent preclinical and clinical investigations that continue to further our knowledge and molecular understanding of the metastatic process with the potential to impact the treatment and improve the prognosis of these patients affected by recurrent disease.

Recently, he presented a study at the 2012 San Antonio Breast Cancer Symposium on commercially-available genomic tests and their ability to better classify tumor subtypes in breast cancer to help guide treatment plans.

“We’re proud that Jefferson is the new home for Dr. Cristofanilli, whose work in cancer research and in the clinic goes unmatched and whose passion to initiate and grow programs speaks for itself, particularly for aggressive forms of breast cancer,” said Neal Flomenberg, M.D., Chair of the Department of Medical Oncology at Jefferson. “We’re looking forward to this new chapter at the Jefferson Breast Care Center and the KCC, where his experience in compassionate clinical care and cutting edge research will better serve the institution and ultimately the patients in the region and beyond.”

Dr. Cristofanilli received his medical degree from the University of La Sapienza in Rome, Italy, where he also completed a fellowship in medical oncology.  He completed an internship at the Cabrini Medical Center in New York, as well as his residency in internal medicine. That was followed by a fellowship in medical oncology at The University of Texas M.D. Anderson Cancer Center.

Dr. Cristofanilli is Board Certified by the American Board of Medical Oncology and the European Society for Medical Oncology.

“Jefferson, as an institution, has a tradition, but at the same time is always projecting towards the future, forever expanding upon research and clinical programs, bringing innovative technologies into the lab and clinic, and attracting new physicians and patients,” said Dr. Cristofanilli. “I want to bring my vision to Jefferson and look forward to us to being able to grow together.”

The Jefferson Breast Care Center was founded in 2006 and is one of 466 centers in the nation accredited by the National Accreditation Program for Breast Centers. The Center gives the patient a comprehensive experience where surgery, medical oncology, radiation oncology, radiology, pathology risk assessment / genetics, social work and a breast care navigator are all working together with the patient at the center of care.



Jefferson Opens Calorie Restriction Trial for Early Stage Breast Cancer Patients on Radiation Therapy

Nicole Simone, M.D.

Jefferson’s Kimmel Cancer Center will begin a first-of-its-kind clinical trial that uses calorie restriction to help treat early stage breast cancer patients undergoing radiation therapy.

Evidence suggests that reducing patients’ calorie intake could help shrink tumors and improve survival because it enhances the effectiveness of radiation therapy, the team explains in a recent review published in the Oncologist.

“In our research, we’ve seen a 30 percent reduction in tumor size in mice, and they live much longer than mice not on a diet,” said Nicole Simone, M.D., Principal Investigator and Assistant Professor of Radiation Oncology at Thomas Jefferson University and Hospitals. “The next step is to investigate if early stage breast cancer patients are able to adhere to caloric restriction while on radiation. This will then allow us to determine others benefits and factors, such as toxicity, recurrence, and survival.”

Until now, the use of calorie restriction to treat cancer or augment standard cancer treatment, such as radiation therapy, has received little attention, with few trials underway in the U.S. Jefferson’s trial, however, is the first in breast cancer patients.

The study is being partly funded by a donation from the Ladies of Port Richmond, a local breast cancer group that raises awareness and funds for research.

Caloric restriction has been shown to alter molecular pathways that make cancer cells more susceptible to radiation, enhancing its effectiveness and thus shrinking tumors and improving survival in mice. What’s more, clinical evidence over the last several decades has shown a link between cancer incidence and calorie restriction.

Beginning in February, Jefferson will begin enrolling 40 women on a calorie reduction diet (a 25 percent reduction of the patients typical total intake) while undergoing treatment. Stage 0 and I breast cancer patients who are not diabetic but who are candidates for breast conserving therapy will be given dietary counseling and guidance to carry out a liquid diet 36 hours prior to lumpectomy and then a calorie reduction of 25 percent will be done during radiation therapy.

Calorie restriction will start the week of radiation planning and continue for the six weeks of radiation, for a total of 10 weeks. Patients will keep a nutritional journal, have counseling in Jefferson’s own Myrna Brind Center of Integrative Medicine to tailor the diet reduction for each individual patient and also meet with counselors during weekly visits.

For the trial, the feasibility of treating breast cancer patients with a calorie-restriction diet modification in conjunction with standard radiation will be assessed. Acute toxicity as per National Cancer Institute Common Toxicity Criteria, quality of life, local recurrence, progression-free survival, distant metastases and overall survival will be also assessed.

In the lab, calorie restriction has been used prior to implantation of tumor cells in mouse breast cancer models and has been shown to slow or even prevent tumor growth.

Dr. Simone’s laboratory has investigated calorie restriction as a treatment modality, implanting tumors in mice prior to initiation of the diet to mimic the use of a diet in a newly diagnosed patient. For the second approach, calorie restriction was administered with cytotoxic therapy to determine the value of calorie restriction as part of a combination therapy.

Preliminary data demonstrated that calorie restriction repressed tumor growth when administered concurrently with radiation in two types of breast cancer: triple negative breast cancer, which has a propensity for metastases and locally aggressive breast cancer.

Calorie restriction alters molecular pathways, including the insulin and AMP-kinase pathway, the researchers posit, leaving cancer cells more sensitive to radiation therapy. Both pathways have been shown to play a role in breast cancer cell proliferation and progression of disease.

Dr. Simone presented the work at the 2012 American Society for Radiation Oncology, and has published several studies on the topic in Cell Cycle and International Journal of Breast Cancer

“Dieting is likely an effective method to enhance the cytotoxicity of radiation therapy because of the overlapping induction of molecular profiles, and it may also provide a beneficial means of improving the overall health and metabolic profiles of patients,” said Dr. Simone. “This trial could provide evidence to implement calorie restriction into the care of cancer patients in treatment. What’s more, it may provide a cost-effective addition to current treatment modalities that enhances cancer therapy while minimizing side effects.”



Jefferson Radiation Oncology Resident Looks to Improve Prostate Cancer Outcomes in Ghana

Kosj Yamoah, M.D., Ph.D.

A new study published in January in the journal BMC Cancer, led by Kosj Yamoah, M.D., Ph.D., a resident in the Department of Radiation Oncology at Thomas Jefferson University and Hospital, takes aim at the issue by investigating prostate cancer diagnoses and treatment delivery in black men living in the West African region, in order to devise research strategies to help improve health outcomes.

Overall, many men are diagnosed at a later stage, with more than half opting out of treatment, they found. The researchers point to stigmas about cancer as a root of the problem.

“Cancer could eclipse infectious diseases as an epidemic if more awareness and intervention doesn’t come about,” said Dr. Yamoah, who grew up in Ghana until age 20, when he came to the United States. “Cancer can be very hush-hush because of cultural and financial issues and social stigmas associated with the disease. We need to bring awareness and address the needs of the population and barriers to care.”

“Cancer is still perceived as a death sentence,” he added. “People are scared to go to their doctor to find out if they have it, let alone to follow through with treatment.”

In a retrospective analysis of 379 patients referred for treatment at the National Center for Radiotherapy and Nuclear Medicine at the Korle Bu Teaching Hospital (KBTH) from 2003 to 2009, the team found that 33 percent were diagnosed with metastatic disease and 70 percent had a prostate-specific antigen (PSA) score four times higher than men in the United States or Europe at time of diagnosis.

PSA screening rates in Ghana are low, the authors explain, and many men opt out of radiation therapy and other therapies after diagnosis. Out of the 251 patients eligible for radiation therapy, only 141 patients actually received external beam radiation therapy.

Among patients with at least two years of follow up after external beam radiation therapy, three- and five-year PSA-failure free survival was 73.8 percent and 65.1 percent respectively. In the U.S., those percentages are 90 percent and 85 percent, respectively.

Reasons recognized by KBTH clinicians for patients declining radiation therapy included: the prohibitive cost of treatment, fear of radiation, and a state of denial based on their perception of disease originating solely from spiritual causes rather than biologic processes.

The data, which to date provides the largest source of published information on outcomes for prostate cancer treatment in the West African region, is a call to action, according to the authors.

The research team plans to develop treatment regimens tailored to the needs of Ghanaian men, which may differ from guidelines currently utilized in the Unites States and Europe in order to better address the disease burden and improve mortality rates in Ghana. That could mean more frequent PSA screening.

“There is controversy in the United States with PSA testing, but in a country like Ghana, there may be a role for PSA screening, even infrequent screening, because of all the late stage cancers we are finding,” said Dr. Yamoah.

The team has established collaboration between two institutions with the hope of improving prostate cancer treatment and plan to start more clinical trials to develop novel, shorter course treatments for locally-advanced prostate cancer.

“Based on these results, our group has proposed a plan for future research aimed at identifying an appropriate role for PSA screening in this population, developing radiation therapy treatment schedules that better fulfill the needs of Ghanaian prostate cancer patients, and contributing to understanding genetic factors associated with prostate cancer risk and treatment response,” the authors write.

Sarah E. Hegarty, a statistical analyst in the Department Pharmacology & Experimental Therapeutics at Jefferson, and Terry Hyslop, Ph.D., also of the Department Pharmacology & Experimental Therapeutics at Jefferson, were also part of the study.



Phone and Mailed Interventions Significantly Increase Colorectal Cancer Screening Rates

Ronald Myers, Professor of Medical Oncology

A mailing or phone call to help patients get screened for colorectal cancer significantly increases their chances of actually getting tested, according to a study published in the January issue of Cancer Epidemiology, Biomarkers and Prevention by researchers at the Kimmel Cancer Center at Jefferson.

The research team, led by Ronald E. Myers, Ph.D., Professor and Director of Division of Population Science, Department of Medical Oncology at Thomas Jefferson University, performed a randomized, controlled trial of 945 people aged 50-79 to test the impact of a new, preference-based navigation intervention, as opposed to standard mailing or usual care, on screening rates.

A third of the patients received a “tailored” phone call to encourage them to perform their preferred screening test (colonoscopy vs. at-home blood stool test), plus a mailing of preferred information; another third were sent information on colonoscopy and a stool blood test kit; while the last third received no intervention.

Patients who received a phone call and/or mailing were almost three times as likely to undergo screening six months later compared to those who had no intervention. However, there was no significant difference between the phone and mailed interventions versus mailings only on screening rates.

While colorectal cancer screening rates are increasing in the United States, rates lag behind those for breast and cervical cancer screening. Screening and early detection of colon and rectal cancer holds tremendous promise for reducing the toll of colon and rectal cancer.

Colorectal cancer is the third leading cause of cancer death in this country with more than 140,000 new cases diagnosed each year. Late diagnoses will account for many of the colorectal cancer related deaths.

The study, which was conducted between 2007 and 2011, included 10 primary care practices affiliated with the Christiana Care Health System in Delaware that used a comment medical record system.

The research team searched for patients who had no prior diagnosis of colorectal neoplasia or inflammatory bowel diseases, had visited one of the participating practices within the previous two years, and were not compliant with American Cancer Society colorectal cancer screening guidelines.

For the study, 312 patients received a tailored intervention, where they were informed about both colonoscopy and blood stool tests and then were sent information on colonoscopy or the actual blood test performed, based on their preference. Another group, consisting of 316 patients, was mailed information about both colonoscopy and stool blood test performed.  The remaining 317 were sent no information or tests and did not receive any phone calls.

Overall screening adherence at six months was significantly higher in both invention groups compared to the control group, the researchers found. Thirty-eight percent of patients who received the tailored phone interventions and 33 percent of patients who received mailings completed screening tests. Only 12% of patients in the control group completed screening tests.

In terms of the intervention groups, the researchers found that preference-based navigation did not significantly boost overall adherence to a level that was significantly higher than that achieved by mail, but increased participant performance of their preferred screening test in comparison to the mailed intervention, especially colonoscopy use.

“The study showed that both strategies were superior to usual care, and that there is not a one-size fits all approach to screening,” said Dr. Myers. “The next step is to determine if an intervention strategy that maximizes screening test access, incorporates patient preference, and engages providers can achieve higher screening rates compared to just mailings.”



Radiation Oncology Services Expanding at Riddle Hospital

Jefferson Radiation Oncology at Riddle Memorial Hospital is pleased to announce that the expansion of Radiation Oncology services has begun.

In the next few months, the Department will begin installing a new True –Beam linear accelerator, Brachytherapy High Dose Rate machine and a CT scanner.

Construction is expected to be completed by December 2013.

The acquisition of this new technology at Riddle Hospital will allow Jefferson physicians to offer the latest cancer treatment techniques, while utilizing state-of-the-art equipment.

Riddle Hospital offers a wide variety of cancer services including support groups, free cancer screenings, diagnostic techniques, treatments and educational programs, to name a few.

For more information, visit http://www.kimmelcancercenter.org/jkccn/members/riddle-memorial-hospital.html



Karen Knudsen, Ph.D., Appointed Deputy Director of Basic Science at Thomas Jefferson University

Thomas Jefferson University and the Kimmel Cancer Center are pleased to announce that Karen E. Knudsen, Ph.D., has accepted the position as Deputy Director of Basic Science, and will hold the prestigious Hilary Koprowski Chair in the Department of Cancer Biology.

Dr. Knudsen received her Ph.D. from the University of California at San Diego in 1996, focusing on cell cycle checkpoint control.  Her postdoctoral studies with Dr. Webster K. Cavenee at the Ludwig Institute for Cancer Research cultivated a program centered on the mechanisms underlying hormone-dependent cell cycle control.

Dr. Knudsen was recruited to Thomas Jefferson University in 2007 (now a Professor in the Departments of Cancer Biology, Urology, & Radiation Oncology) after a successful career at the University of Cincinnati College of Medicine, where she was a tenured Associate Professor.  In addition to her duties as the Deputy Director, Dr. Knudsen also serves as Leader of the Kimmel Cancer Center Biology of Prostate Cancer Program, and Director of the Greater Philadelphia Prostate Cancer Working Group.

Dr. Knudsen’s research interests are dedicated to understanding the mechanisms by which hormone receptor and cell cycle deregulation lead to prostate cancer progression and therapeutic bypass.  The overall goal of Dr. Knudsen’s laboratory is to utilize this information for successful development of precision medicine, so as to improve therapeutic outcome and patient care through rational therapy delivery.  Her studies identifying tumor suppressor and hormone receptor alterations have uncovered new targets for treating advanced disease, and led to development of biomarker-driven clinical trials.

Dr. Knudsen serves on a multitude of national boards and committees, including those for the American Association for Cancer Research, the Endocrine Society, and the Prostate Cancer Foundation.  She has been a Senior Editor for Cancer Research since 2007, is an Associate Editor for Endocrine-Related Cancer, and sits on the editorial boards of Molecular Cancer Therapeutics, the American Journal of Pathology, Molecular Endocrinology, and Oncogene. Most recently, Dr. Knudsen was appointed Editor-in-Chief of Molecular Cancer Research by the American Association for Cancer Research.  Dr. Knudsen has received numerous awards for her research, including the Ronald Ross Award for Excellence in Hormone-dependent malignancies from the Pacific Rim Breast and Prostate Cancer Research Organization, and the Richard E. Weitzman Laureate Award from the Endocrine Society.



Bench to Bedside: How to Fast Track Targeted Cancer Drugs with Radiation into the Clinic

Researchers from the translational research program of the National Cancer Institute and the Radiation Therapy Oncology Therapy Group have developed new guidelines to help fast track the clinical development of targeted cancer drugs in combination with radiation therapy.

The suggested strategic guidelines, published in the Journal of the National Cancer Institute in a recent commentary with lead author Yaacov Richard Lawrence, MRCP, an adjunct Assistant Professor in the Department of Radiation Oncology at Thomas Jefferson University and Director of the Center for Translational Research in Radiation Oncology at Sheba Medical Center in Israel, offers specific steps in the preclinical and early phase clinical trial process to get well-studied and novel targeted agents into the clinic more quickly.

Over the last decade, molecular agents that target cellular survival and growth, like Erlotinib and Sunitinib, have been developed but alone have had modest effect on improved survival. Combining such targeted agents with radiation therapy, however, has the potential to improve cure rates and long-term overall survival.

“There’s a missed opportunity in today’s cancer care treatment,” says Dr. Lawrence. “There is very promising laboratory data out there, but the clinical development of these new drugs with radiation has been limited. Here, we have put together a road map to help overcome obstacles and speed the development of new pipeline drugs with radiation.”

Adding radiation therapy to existing chemotherapy agents to radiation therapy has improved survival, and the authors of the commentary, which includes Adam P. Dicker, Chair of the Department of Radiation Oncology at Jefferson, believe new targeted therapies can follow in the same path.

“We know we want to repeat that success with new biological drugs,” says Dr. Lawrence. “In order to do that, we need direction, which is sorely lacking. These guidelines explicitly explain how much evidence is needed to go forward from the lab into the clinic, and furthermore how to design the clinical trials in humans.”

The guidelines discuss key questions when investigating specific targeted agents and tumor types, designing new clinical trials, such as the ‘time-to-event continual reassessment method design’ for phase I trials, and randomized phase II “screening” trials, and the use of surrogate endpoints, such as pathological response.

It also discusses the role and purpose of preclinical studies in radiation oncology drug development and how to identify new, radiation response agents.

There are challenges to drug development with radiation, the authors explain. A major problem is the limited interest from the pharmaceutical industry in developing drugs with radiation, which is of special importance since the pharmaceutical industry fund a large amount of clinical cancer research. Furthermore, significant individual skills and institutional commitments are also required to ensure a successful program. The situation has been extenuated by the decrease in radiation biologists in recent years.

It is hoped that by providing a clear pathway, the guidelines will help the field overcome these barriers and create a focus and interest in drug development.
Some new approaches, the researchers say, include combining radiosensitizers with hypofractionated (high daily dose) radiation schedules and integrating immunomodulators with radiation therapy.

“We feel passionate that a a good way to push clinical care forward for cancer patients is by combining these two types of treatment: advanced radiation treatment together with the new generation of anticancer drugs,” says Dr. Lawrence. “We know where the future lies, and guidelines provide the path to bring us there.”

The full guidelines in the JNCI can be found here: http://jnci.oxfordjournals.org/content/early/2012/12/07/jnci.djs472.full



More Designated Time Equals More Published Research for Radiation Oncology Residents

What helps radiation oncologist residents publish more academic research?

Giving them more time to do it, physicians in the Department of Radiation Oncology at Thomas Jefferson University Hospital conclude in a study published recently in the Journal of American College of Radiology.

Based on results from a web-based survey completed by 97 radiation oncologists and current senior residents from academic medical centers across the country, the biggest factor contributing to more first-author publications for residents is the amount of designated research time given during residency.

Anecdotally, there seems to be much variability in the productivity of radiation oncology residents. Some publish numerous articles, whereas others produce less. However, what leads to this variability remains undefined.

It appears that previous individual accomplishments or values among residents—often thought of as critical factors—seem to play less of a role than time and structure of a program.

To determine the predictors, researchers from Jefferson and Drexel University College of Medicine, invited 232 radiation oncologists and senior residents to partake in the web-based survey.

The survey addressed demographic factors, previous academic accomplishments, and residency program structure. The end point—research productivity—was defined as the number of first-author papers produced or research grants awarded on the basis of work initiated during residency.

There was a 42 percent response rate, most of whom were women. The median number of publications produced on the basis of work during residency was three. The average amount of dedicated research time was six months. 16 percent had less than three months. The more time a resident had, the more papers they published.

The results imply that academic success is not simply the result of innate ability but rather the structural aspects of residency programs.

“Medical research by residents is an important part of training, contributes to the academic growth of the radiation oncology field, and ideally makes them better physicians,” said Robert B. Den, M.D., Assistant Professor of Radiation Oncology at Jefferson and author of the paper.  “The structure of a program highly influences resident research capability,” he added.

Other authors on the paper includes Jordan M. Gutovich of Drexel University, Maria Werner-Wasik, M.D., Associate Professor of Radiation Oncology at Jefferson, Adam P. Dicker, M.D., Ph.D., Chair of Radiation Oncology at Jefferson, and Yaacov Richard Lawrence, MRCP, an adjunct Assistant Professor in the Department of Radiation Oncology at Jefferson University and director of the Center for Translational Research in Radiation Oncology at Sheba Medical Center in Israel.

The full study can be found here: http://www.jacr.org/article/S1546-1440%2812%2900386-9/abstract



Game changing diagnostic & prognostic prostate cancer genetic tests revealed by KCC researchers

Richard Pestell, M.D., Ph.D.

Researchers at the Kimmel Cancer Center at Jefferson (KCC) have developed potentially game-changing diagnostic and prognostic genetic tests shown to better predict prostate cancer survival outcomes and distinguish clinically-relevant cancers.

The team, led by Richard G. Pestell, M.D., Ph.D., Director of the KCC and the Chair of the Department of Cancer Biology at Thomas Jefferson University, report their preclinical findings from a blinded, retrospective analysis of over 350 patients and mouse study in a recent issue of the journal of Cancer Research.

Using an oncogene-specific prostate cancer molecular signature, the researchers were able to separate out men who died of prostate cancer versus those who lived, and more specifically, identifying men who died on average after 30 months (recurrence free survival). The diagnostic test distinguished patients with clinically relevant prostate cancer from normal prostate in men with elevated prostate-specific antigen (PSA) levels.

The researchers worked with three oncogenes previously associated with poorer outcomes in prostate cancer: c-Myc , Ha-Ras, and v-Src.

The test, the researchers say, is superior to several previously published gene tests and to the Gleason scale, which is a rating given to prostate cancer based upon its microscopic appearance and currently used to help evaluate the prognosis of men with the disease.

Given the diversity of prostate cancer outcomes—some men live two years after diagnosis, others live for more than 20 more years— a new oncogene-specific signature like this could not only help better identify prostate cancer risk but also test targeted therapies—by way of a new prostate cancer cell line.

These studies describe the first isogenic prostate cancer cell lines that metastasize reliably in immune competent mice. Previous studies were in immune deficient mice.

“This oncogene signature shows further value over current biomarkers of prediction and outcomes,” said Dr. Pestell. “Such a signature and cell line may also enable the identification of targets for therapies to better treat prostate cancer, which takes the lives of over 27,000 men a year.”

In breast cancer, the identification of tumor subsets with various gene signatures has improved clinical care for patients because of targeted therapies.

The work here by the KCC aims to identify gene patterns and subsequent tests in prostate cancer that could serve similar purposes. But to help develop such therapies, model systems that closely resemble human disease are required. To date, there have been several limitations with currently available cell lines.

Although important transplantation experiments have been conducted using human prostate cancer cell lines in immune deficient animals, the immune system plays an important role in prostate cancer onset and progression making it imperative to develop prostate cancer cell lines that can be studied in immune competent animals.

Also, although the transgenic mouse has been an effective model to study the molecular basis of human cancers, the prostate cancer mouse models have long latency and often unpredictable metastasis.

Here, the researchers succeeded in overcoming these issues.

The oncogene-specific prostate cancer molecular signatures were recapitulated in human prostate cancer and validated in distinct populations of patients as a prognostic and diagnostic test.

What’s more, the researchers demonstrated how the isogenic prostate cancer cell lines metastasized in immune-competent mice.

“Identification of gene signatures in breast cancer has allowed for a deeper understanding of the disease, and this paper moves us steps closer to being able to follow a similar trajectory with prostate cancer. Today, such an understanding and a formidable testing ground for new therapies is lacking for this disease,” Dr. Pestell said. “With this new oncogene-specific prostate cancer molecular signature, we have a valuable prognostic and diagnostic resource that could help change the way we manage and treat prostate cancer.”

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Other researchers in the study include Xiaoming Ju, Adam Ertel, Mathew Casimiro, Zuoren Yu, Hui Meng, Peter A. McCue, Rhonda Walters, and Paolo Fortina.



KCC researchers discover new pathways that drive metastatic prostate cancer

Karen Knudsen, Ph.D.

Elevated levels of Cyclin D1b could function as a novel biomarker of lethal metastatic disease in prostate cancer patients, according to a pre-clinical study published ahead of print on December 21 in the Journal of Clinical Investigation by researchers at the Kimmel Cancer Center at Jefferson.

The group, headed by Karen E. Knudsen, Ph.D., Professor and Hilary Koprowski Chair, Departments of Cancer Biology, Urology, and Radiation Oncology at Thomas Jefferson University and Deputy Director for Basic Science at the KCC, found that Cyclin D1b, a variant of the cell cycle regulator Cyclin D1a, functions independently of the cell cycle to promote metastasis in both early and late stage prostate cancer.

Rather, Cyclin D1b, but not Cyclin D1a, regulates a large gene network, the researchers found, which was shown to cooperate with androgen receptor (AR) signaling to fuel metastatic progression in multiple models of prostate cancer.

Studies have shown that Cyclin D1b expression is elevated in early stages of prostate cancer (in up to 30% of primary disease), and researchers have now demonstrated that this occurs more frequently in late stage castration-resistant prostate cancer: up to 80%.

Cyclin D1b expression is also highly correlated with that of the pro-metastatic gene SNAI2 (Slug), which the group identified as regulated by cooperative signaling between Cyclin D1b and AR.

“Numerous clinical and pre-clinical studies have effectively demonstrated that AR signaling is critical for progression to metastatic disease, but our knowledge of AR targets which can induce metastatic phenotypes is limited,” said Dr. Knudsen. “Our data describe how cross talk between the cell cycle and AR can rewire the AR signaling axis to enhance the expression of genes which elicit metastasis in both early and castration resistant prostate cancer models.”

“We found that Cyclin D1b can directly promote AR dependent expression of the gene SNAI2 (Slug), which dramatically increased metastatic events to soft tissues in animal models,” she added.

Metastatic castration resistant prostate cancer represents the most lethal form of the disease, which arises when AR is reactivated despite continued hormone therapy.

Soft tissue metastasis to the liver and lung represents a particularly aggressive form of prostate cancer, whose presence predicts for decreased survival time in prostate cancer patients.

Currently, there is little knowledge as to how these metastatic events occur, and identification of pathways and biomarkers of this lethal event could greatly benefit prostate cancer patients.

Using various in vitro and in vivo models, researchers found that Slug enhances the ability of cells to colonize soft tissues, which resulted in a higher incidence of metastasis in the liver and lung.

Given the inability to manage AR signaling in metastatic castration resistant prostate cancer, Slug driven pathways could be leveraged to dramatically limit the incidence of soft tissue metastasis and improve patient morbidity and mortality, researchers believe.

“Identification of AR driven pathways which mediate metastatic progression represents a significant leap forward in our attempts to effectively manage prostate cancer progression,” said Dr. Knudsen. “Cyclin D1b and Slug can likely be used as biomarkers to identify patients with an increased risk of metastasis, and will eventually provide us with novel “druggable” targets downstream of AR and Slug which can be exploited to dramatically reduce the incidence of these lethal metastatic tumors.”

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This study was completed as a result of an inter-institutional team effort, including the contributions of the lead author and graduate student Michael A. Augello of the Department of Cancer Biology at Thomas Jefferson University, as well as key collaborators: Dr. Felix Feng (University of Michigan), Dr. Alessandro Fatatis (Drexel University), Dr. Tapio Visakorpi (University of Tampere), Dr. Donald McDonnell (Duke University), Dr. C. Burd (University of Ohio), Dr. D E. Frigo (University of Houston) and Dr. Ruth Birbe of Thomas Jefferson University.



Edith Mitchell Appointed to NCI’s Clinical Trials & Translational Research Advisory Committee

Edith P. Mitchell, M.D., FACP, a medical oncologist at Thomas Jefferson University Hospital and Clinical Professor of Medicine and Medical Oncology in the Department of Medical Oncology at Jefferson Medical College of Thomas Jefferson University, has been appointed to the National Cancer Institute’s Clinical Trials and Translational Research Advisory Committee.

Dr. Edith Mitchell

The committee makes recommendations on the NCI-supported national clinical trials enterprise to build a strong scientific infrastructure by bringing together a broadly developed and engaged coalition of stakeholders involved in the clinical trials process. This encompasses oversight of all trials both extramural and intramural.

The committee will also provide broad scientific and programmatic advice on the investment of tax payer dollars in clinical trials and supportive science. This will lead to enormous potential for more specific cancer treatment, coupled with the complexity of evaluating new, highly specific agents integrating knowledge, insights, and skills of multiple fields into a new kind of cross-disciplinary, scientifically-driven, cooperative research endeavor.

The Committee will consist of 25 members.

Congratulations to Dr. Mitchell on this appointment.



ACS-IRG Pilot Projects Awarded for 2012

The Kimmel Cancer Center at Jefferson hosted the Annual ACS-IRG Luncheon on November 11. The 2012 Pilot Project recipients are S. Onder Alpdogan, MD; Amy Leader, DrPh, MPH; and Jianqing Lin, MD; all of the Department of Medical Oncology; Scott Keith, PhD; from the department of Pharmacology & Experimental Therapeutics; Nicole Simone, MD; department of Radiation Oncology; and Christopher Snyder, PhD; department of Microbiology & Immunology. They briefly explained their research projects to Lynne Ayres, MBA, Director of Research Communications, and Larry Slagle, Distinguished Giving Director, of the East Central Division of the American Cancer Society. Ms. Ayres and Mr. Slagle explained the ACS mission and offered ways in which the Pilot Project recipients would be able to assist them in that mission.

Left to Right: Nicole Simone, Jianqing Lin, Marja Nevalainen, Larry Slagle, Lynne Ayres, Christopher Snyder, Amy Leader, and Scott Keith.




Kimmel Cancer Center “All Hands Meeting”

The Kimmel Cancer Center held it’s quarterly “All Hands” meeting on December 12, 2012. Dr. Richard Pestell, Director of the Kimmel Cancer Center, delivered his quarterly “State of the Cancer Center” address. Awards were presented in 3 categories. The Administration Award was presented to the KCC Post-Award Administration Group (Dina Liebowitz, Melissa McDaid Dyer, Melanie Elliott, Karen Gosik, Tracey Kajkowski, Kathy Wyszynski, Rick Yellis and Pam Bachman). The Nursing Award was presented to Bone Marrow Transplant Unit (Patricia Cornett Farley, Michael Sun, Ngoc Bao Ho, Minh Duc Tran, Brendan McGuire and Barbara Stanback). The Clinical Award was presented to Matthew Carabasi, MD. There were also special presentations about upcoming Consortium-wide Pilot/Special Project Funding opportunities. Dr. Richard Davidson discussed the American Cancer Society – Institutional Research Grant. Drs. Andrew Quong and Noreen Robertson discussed the KCC Pilot Project Program (funding provided by TJU and Drexel). Dr. Banu Onaral and Mr. Davood Tashayyod discussed the Wallace H. Coulter Foundation Translational Research Partnership Program.

Dr. Matthew Carabasi receives the Clinician Award from Drs. Neal Flomenberg and Richard Pestell

The Bone Marrow Transplant Unit receives the Nursing Award from Drs. Neal Flomenbger and Richard Pestell



Kimmel Cancer Center “All Hands Meeting”

The Kimmel Cancer Center held it’s quarterly “All Hands” meeting on September 12, 2012. Dr. Richard Pestell, Director of the Kimmel Cancer Center, delivered his quarterly “State of the Cancer Center” address. Awards were presented in 4 categories. The Administration Award was presented to Janene Palidora. The Nursing Award was presented to Cheryl Santosusso. The Clinical Award was presented to Vochita Bar Ad, MD. The Basic Science/”Discovery of the Year” Award was presented to George Prendergast, PhD. In addition to the KCC Awards, the “Distinguished Mentor” Award was presented to Karen Knudsen. PhD by the Jefferson College of Graduate Studies Office of Postdoctoral Affairs and the Jefferson Postdoctoral Association. Dr. Renato Iozzo also received the “Distinguished Mentor” award. See JCGS Page for more

Dr. Noreen Robertson receives the Administration Award from Drs. Richard Pestell and Richard Davidson

Ms. Janene Palindora receives Administration Award from Mr. Richard Haldeman

Ms. Cheryl Santosusso receives Nursing Award from Dr. Neal Flomenberg

Ms. Cheryl Santosusso receives Nursing Award from Dr. Neal Flomenberg

Dr. Vochita Bar Ad receives the Clinicican Award from Dr. Neal Floimenberg

Dr. George Prendergast receives Basic Science/"Discovery of the Year" Award from Dr. Richard Pestell

Dr. Karen Knudsen receives JCGS "Distinguished Mentor" Award from Dr. Lisa Kozlowski




Kimmel Cancer Center “All Hands Meeting”

The Kimmel Cancer Center held it’s quarterly “All Hands” meeting on June 19, 2012. Dr. Richard Pestell, Director of  the Kimmel Cancer Center, delivered his quarterly “State of the Cancer Center” address. Awards were presented in 3 categories. The Administration Award was presented to Rita Genovese, CPC, PCS. The Basic Science Award was presented to Adam Ertel, PhD. The Nursing Award was presented to Susan Krick, RN. The Clinical Award was presented to Edith Mitchell, MD.

Ms. Rita Genovese receives Administrative Award from Mr. Richard Haldeman

Ms. Susan Krick receives Nursing Award from Dr. Adam Dicker

Dr. Adam Ertel receives the Basic Science Award from Dr. Richard Davidson

Dr. Adam Ertel receives the Basic Science Award from Dr. Richard Davidson