Biomarker Links Clinical Outcome with New Model of Lethal Tumor Metabolism

Researchers at the Kimmel Cancer Center at Jefferson have demonstrated for the first time that the metabolic biomarker MCT4 directly links clinical outcomes with a new model of tumor metabolism that has patients “feeding” their cancer cells.  Their findings were published online March 15 in Cell Cycle.

To validate the prognostic value of the biomarker, a research team led by Agnieszka K. Witkiewicz, M.D., Associate Professor of Pathology, Anatomy and Cell Biology at Thomas Jefferson University, and Michael P. Lisanti, M.D., Ph.D., Professor and Chair of Stem Cell Biology and Regenerative Medicine at Jefferson, analyzed samples of patients with triple negative breast cancer, one of the most deadly of breast cancers, with fast-growing tumors that often affect younger women.

A retrospective analysis of over 180 women revealed that high levels of the biomarker MCT4, or monocarboxylate transporter 4, were strictly correlated with a loss of caveolin-1 (Cav-1), a known marker of early tumor recurrence and metastasis in several cancers, including prostate and breast.

“The whole idea is that MCT4 is a metabolic marker for a new model of tumor metabolism and that patients with this type of metabolism are feeding their cancer cells. It is lethal and resistant to current therapy,” Dr. Lisanti said. “The importance of this discovery is that MCT4, for the first time, directly links clinical outcome with tumor metabolism, allowing us to develop new more effective anti-cancer drugs.”

Analyzing the human breast cancer samples, the team found that women with high levels of stromal MCT4 and a loss of stromal Cav-1 had poorer overall survival, consistent with a higher risk for recurrence and metastasis, and treatment failure.

Applying to a Triple Threat

Today, no such markers are applied in care of triple negative breast cancer, and as a result, patients are all treated the same. Identifying patients who are at high risk of failing standard chemotherapy and poorer outcomes could help direct them sooner to clinical trials exploring new treatments, which could ultimately improve survival.

“The idea is to combine these two biomarkers, and stratify this patient population to provide better personalized cancer care,” said Dr. Witkiewicz

The findings suggest that when used in conjunction with the stromal Cav-1 biomarker, which the authors point out has been independently validated by six other groups worldwide, MCT4 can further stratify the intermediate-risk group into high and low risk.

Since MCT4 is a new druggable target, researchers also suggest that MCT4 inhibitors should be developed for treatment of aggressive breast cancers, and possibly other types.  Targeting patients with an MCT4 inhibitor, or even simple antioxidants, may help treat high-risk patients, who otherwise may not respond positively to conventional treatment, the researchers suggest.

Paradigm Shift

But the work stems beyond triple negative breast cancer, challenging an 85-year-old theory about cancer growth and progression.

This paper is the missing clinical proof for the paradigm shift from the “old cancer theory” to the “new cancer theory,” known as the “Reverse Warburg Effect,” said Dr. Lisanti. The new theory being that aerobic glycolysis actually takes place in tumor associated fibroblasts, and not in cancer cells, as the old theory posits.

“The results by Witkiewicz et al. have prominent conceptual and therapeutic implications,” wrote Lorenzo Galluzzi, Ph.D., Oliver Kepp, Ph.D., and Guido Kroemer, M.D., Ph.D. of the French National Institute of Health and Medical Research and Institut Gustave Roussy, in an accompanying editorial. “First, they strengthen the notion that cancer is not a cell-autonomous disease, as they unravel that alterations of the tumor stroma may constitute clinically useful biomarkers”.

“Second, they provide deep insights into a metabolic crosstalk between tumor cells and their stroma that may be targeted by a new class of anticancer agents.”

Dr. Kroemer entitled his commentary “Reverse Warburg: Straight to Cancer” to emphasize that the connective tissue cells (fibroblasts) are directly “feeding” cancer cells, giving them a clear growth  and survival advantage.  New personalized therapies would cut off the “fuel supply” to cancer cells, halting tumor growth and metastasis.



Kimmel Cancer Center “All Hands Meeting”

The Kimmel Cancer Center held it’s quarterly “All Hands” meeting on March 14, 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/Wings Award was presented to Steven McKenzie, MD, PhD. The Basic Science Award was presented to John Pascal, PhD. The Nursing Award was presented to Deborah Turner, RN. The Clinical Award was presented to Edith Mitchell, MD.

Dr. Steven MCKenzie recieves Administrative/Wings Award from Dr. Richard Pestell

Dr. Steven MCKenzie recieves Administrative/Wings Award from Dr. Richard Pestell

Dr. John Pascal receives the Basic Science Award from Dr. Jeffrey Benovic

Dr. John Pascal receives the Basic Science Award from Dr. Jeffrey Benovic

Ms. Deborah Turner receives Nursing Award from Dr. Neal Flomenberg

Ms. Deborah Turner receives Nursing Award from Dr. Neal Flomenberg

Dr. Edith Mitchell receives Clinician Award from Dr. Neal Flomenberg

Dr. Edith Mitchell receives Clinician Award from Dr. Neal Flomenberg





Kimmel Cancer Center “All Hands Meeting”

The Kimmel Cancer Center held it’s quarterly “All Hands” meeting on December 23, 2011. Dr. Richard Pestell, Director of the Kimmel Cancer Center, delivered his quarterly “State of the Cancer Center” address. Awards were presented in six categories. The Administration Award was presented to Jeanine Voll. The Basic Science Award was presented to Agnieszka Witkiewicz, MD. The Nursing Award was presented to Maura Milligan, RN. The Clinical Award was presented to Nancy Lewis, MD. The “Discovery of the Year” Award was presented to Neal Flomnberg, MD and Dolores Grosso, RN, CRNP, DNP for their work in using haploindentical donors successfully in bone marrow transplants. The “Lifetime Achievement” Award was presented to Renato Baserga, MD.

Dr. Renato Baserga receives the "Lifetime Achievement" Award From Dr. Richard Pestell

Dr. Renato Baserga receives the "Lifetime Achievement" Award From Dr. Richard Pestell

Ms. Jeanine Voll receives Administration Award from Dr. Richard Davidson

Ms. Jeanine Voll receives Administration Award from Dr. Richard Davidson

Dr. Agnieszka Witkiewicz receives Basic Science Award from Dr. Richard Pestell



Dr. Nancy Lewis receives Clinical Award from Dr. Neal Flomenberg

Dr. Nancy Lewis receives Clinical Award from Dr. Neal Flomenberg

Dr. Neal Folmenberg and Dr. Dolores Grosso receive the "Discovery of the Year" Award from Dr. Richard Pestell

Dr. Neal Folmenberg and Dr. Dolores Grosso receive the "Discovery of the Year" Award from Dr. Richard Pestell




Rawls Palmer Progress in Medicine Award Presented to Dr. Scott A. Waldman

Scott A. Waldman, M.D., Ph.D., will receive the American Society for Clinical Pharmacology and Therapeutics (ASCPT) Rawls–Palmer Progress in Medicine Award at the 2012 Annual Meeting on March 16.

Established in 1978 by Dr. W. B. Rawls, the award recognizes scientists who have implemented progressive research techniques and tools to improve patient care.

Scott Waldman, M.D., Ph.D.

ASCPT will present the award to Dr. Waldman prior to his lecture at the 113th Annual Meeting.

Dr. Waldman is the Samuel MV Hamilton Endowed Professor of Medicine, Vice President of Clinical and Translational Research, and Chair of the Department of Pharmacology and Experimental Therapeutics at Thomas Jefferson University. He is also Director of the Gastrointestinal Malignancies Program at the university’s Kimmel Cancer Center and Associate Dean of Clinical and Translational Sciences at Jefferson Medical College.

As a longtime volunteer leader of ASCPT, Dr. Waldman has participated on various committees and task forces, serving on the Board of Directors, as Society president, and as Editor in Chief of Clinical Pharmacology and Therapeutics since 2006.

Dr. Waldman has chaired numerous scientific review panels for the NIH and is on the editorial boards of Personalized Medicine, Expert Reviews in Clinical Pharmacology, and Regenerative Medicine, among others. He is the inaugural Deputy Editor of Clinical and Translational Science and the inaugural Senior Editor of Biomarkers in Medicine.

Dr. Waldman is a recognized clinician–investigator whose research ranges from molecular biology to cancer diagnostics and therapeutics. He received the 2010 ASCPT Henry Elliott Award and the 2011 Pharmaceutical Research and Manufacturers of America Foundation Award in Excellence for Clinical Pharmacology and Therapeutics.

About ASCPT

ASCPT is the leading forum for the discussion, development, and integration of clinical pharmacology in the drug development continuum—from discovery to safe and effective use. Headquartered in Alexandria, Virginia, ASCPT was established in 1900. Today, more than 2,100 ASCPT members are committed to advancing the science of human pharmacology and therapeutics worldwide.

*This release was reprinted with permission from ASCPT.



A New Battlefront: Symposium at Jefferson’s Kimmel Cancer Center to Tackle Geriatric Oncology

Approaches to treating elderly cancer patients are evolving as more of the population ages and the need for specialized care becomes more evident.

To address these issues and others, national thought leaders in geriatric oncology will gather at a unique symposium at the Kimmel Cancer Center at Jefferson (KCC) in Philadelphia on Friday, March 9, 2012, where they will present an overview of the latest advances in the understanding and treatment of cancer in older adults in an effort to impact patient care.

Outside of the annual American Society of Clinical Oncology (ASCO) meeting, this is the first regional symposium of its kind that would be addressing the needs of senior adults.

The all-day symposium, “The New Battlefront: Geriatric Oncology,” part of an annual series at the KCC, will be held at the Bluemle Life Sciences Building on Jefferson’s campus. Co-hosted by the KCC Cancer Network and Rothman Institute at Jefferson, it will provide comprehensive updates on basic science research and the latest updates on chemotherapy, surgery, and radiation in the care of senior adult patients.

Personalized Treatment

Geriatric patients make up 60 percent of new cancer diagnoses and 70 percent of all cancer deaths. And those numbers are expected to increase as the geriatric population doubles in size by 2030.

These patients also often must battle cancer in the context of multiple chronic conditions, decreased organ reserve, and all too often cognitive impairments.  What’s more, there’s currently a shortage of geriatric oncology physicians to treat them.

“Recognizing and addressing the particular co-morbidities, functional, and cognitive concerns, and identifying collaborations with other disciplines will help us better serve the population,” said Andrew E. Chapman, DO, FACP, who directs the KCC’s Senior Adult Oncology Center along with Christine A. Arenson, M.D, of the Department of Family and Community Medicine at Thomas Jefferson University Hospital.

A joint effort between the Departments of Medical Oncology and Family and Community Medicine, Division of Geriatrics, KCC’s Senior Adult Oncology Center provides a comprehensive assessment, usually during a single visit, to identify problems related to aging and cancer.   The program has medical oncologists, a geriatrician, a nurse navigator, a pharmacist specially trained in oncology and geriatrics, a registered dietician, and a social worker.

Facing this New Battlefront Together

During the symposium, the full spectrum of geriatric oncology care and research will be discussed by clinicians and researchers from top institutions, including Jan van Duersen, Ph.D., of the Robert and Arlene Kogod Center on Aging at the Mayo Clinic in Rochester, Minn., and Arati V. Rao, M.D. of Duke University’s Division of Geriatrics.

The conference will provide an overview of the biology of cancer in aging, describe the state-of-the-art model of Shared Care for older cancer patients, and review critical issues of chemotherapy toxicity and optimal chemotherapy management.

Specific concerns for radiation therapy and surgery in the geriatric oncology patient will be also addressed. Finally, the latest advances in the management of hematologic and solid malignancies in the elderly will be shared.

Several of the talks also directly address patient and medication safety and improving communication among physicians, patients and other health care personnel.

Discussions will also focus on safe and effective use of chemotherapy and pharmacology safety issues, with talks by Arti Hurria M.D., director of the Cancer and Aging Research Program at the City of Hope National Medical Center and Stuart M. Lichtman, M.D., Professor of Medicine, 65+ Geriatric Clinical Program at Memorial Sloan-Kettering Cancer Center.

John A. Abraham, M.D., Chairman of the Division of Orthopedic Oncology at the Rothman Institute at Jefferson, will also speak about managing orthopedic issues in geriatric oncology patients.

“This symposium is an opportunity for players in the geriatric medicine and oncology, surgery and radiation fields to come together and highlight the innovative discoveries and best practices we believe will be important for the next generation of treatment and therapeutics in patients,” said Richard Pestell, M.D., Ph.D., director of the KCC and Professor and Chair of the Department of Cancer Biology at Jefferson Medical College of Thomas Jefferson University.

Other speakers include Rani P. Anné, M.D., Associate Professor of Radiation Oncology, Clinical Program Director at Jefferson Medical College at Thomas Jefferson University; William Dale, M.D., Ph.D., Chief of Section of Geriatrics and Palliative Medicine at University of Chicago Medical Center; Elizabeth M. Gore, M.D., Associate Director, Radiation Oncology at Medical College of Wisconsin; Supriya Gupta Mohile, M.D., M.S., Associate Professor of Medicine, Hematology/Oncology, University of Rochester Medical Center; Richard C. Wender; Alumni Professor and Chair, Family and Community Medicine, Jefferson Medical College; and Michael Zenilman, M.D., Professor of Surgery, Vice Chair and Director, National Capital Region, Johns Hopkins Medicine.

To register for the event, please visit http://www.kimmelcancercenter.org/symposium/



PCF Young Investigator Award Goes to Jefferson Researcher

Heather Montie, Ph.D., a post-doctoral research fellow in the Department of Biochemistry and Molecular Biology, has received a Prostate Cancer Foundation Young Investigator Award for her work with androgen receptor (AR) acetylation and its role in castration-resistant prostate cancer.

Young Investigator awards are designed to promote long-term careers in the field of prostate cancer by providing three year grants for transformational research focused on prostate cancer treatments to improve patient outcomes. Since 2007, PCF has invested more than $20 million in Young Investigator grants.

“PCF-supported young investigators have changed the scope of prostate cancer research, advancing treatment sciences and improving the lives of patients worldwide,” said Howard Soule, PhD, chief science officer and executive vice president of PCF. “It is with great pride and appreciation that PCF can now announce our young investigator program spans across six countries and 42 research institutes.”

Prostate cancer is driven by the male hormones, androgens which mediate their activity through the androgen receptor. Unfortunately most prostate cancerous tumors progressively become resistant to the preferred treatment modality, androgen deprivation therapy. One of the mechanisms proposed to enhance the activity of androgen receptors in castration-resistant prostate cancer, even in the absence of androgens, is the addition of a small chemical group/moiety to the AR protein. This modification of AR is termed ‘acetylation’ and is proposed to convert the protein to a ‘super AR.’

However, there is currently no experimental data to show that AR acetylation directly enhances AR-dependent prostate cancer cell viability.

Dr. Montie proposes to evaluate the role of AR acetylation in the enhanced AR functional activity central to CRPC. She will study the precise mechanisms by which this modification of AR enhances its cancer-promoting activity. Dr. Montie will also validate the potential of AR acetylation as a therapeutic target for castrate-resistant prostate cancer.

A total of 15 competitive research grants have been awarded to-date in 2012, bringing the total of young investigators awarded to 89.

Each Young Investigator recipient is awarded $225,000 over a three-year period.

Dr. Montie received the 2012 John A. Moran PCF Young Investigator Award. 

Visit here for more on the Young Investigator awards.



Dr. Renato V. Iozzo receives an honorary degree from Semmelweis University in Budapest, Hungary

Congratulations to Renato V. Iozzo, M.D., a Professor of Pathology and Cell Biology, and Professor of Biochemistry & Molecular Biology, Thomas Jefferson University, for receiving an honorary degree (Doctor Honoris Causa) from Semmelweis University in Budapest, Hungary.

Dr. Iozzo received this award in November 2011 in recognition for his contributions to the field of Matrix Biology, Cancer and Angiogenesis.

His research focuses on the biology of proteoglycans and their roles in cancer and angiogenesis, and has published over 275 peer-reviewed articles, numerous reviews and edited two books on proteoglycans.

After receiving an M.D. degree summa cum laude from the University of Florence, Italy, Dr. Iozzo moved to the Department of Pathology at the University of Washington, where he completed a five-year Residency/Fellowship. Following a six-year faculty appointment at the University of Pennsylvania, he was promoted to Associate Professor and then moved the same year to Thomas Jefferson University as Full Professor with tenure.

Founded in 1769 by Maria Theresa the Empress of Austria-Hungary, Semmelweis University is one of the oldest universities and medical schools in Europe.



Stronger Intestinal Barrier May Prevent Cancer in the Rest of the Body, New Study Suggests

Scott Waldman, M.D., Ph.D., chair of the Department of Pharmacology and Experimental Therapeutics at Jefferson and director of the Gastrointestinal Cancer Program at Jefferson’s Kimmel Cancer Center

A leaky gut may be the root of some cancers forming in the rest of the body, a new study published online Feb. 21 in PLoS ONE by Thomas Jefferson University researchers suggests.

It appears that the hormone receptor guanylyl cyclase C (GC-C)—a previously identified tumor suppressor that exists in the intestinal tract—plays a key role in strengthening the body’s intestinal barrier, which helps separate the gut world from the rest of the body, and possibly keeps cancer at bay. Without the receptor, that barrier weakens.

A team led by Scott Waldman, M.D., Ph.D., chair of the Department of Pharmacology and Experimental Therapeutics at Jefferson and director of the Gastrointestinal Cancer Program at Jefferson’s Kimmel Cancer Center, discovered in a pre-clinical study that silencing GC-C in mice compromised the integrity of the intestinal barrier.  It allowed inflammation to occur and cancer-causing agents to seep out into the body, damaging DNA and forming cancer outside the intestine, including in the liver, lung and lymph nodes.

Conversely, stimulating GC-C in intestines in mice strengthened the intestinal barrier opposing these pathological changes.

A weakened intestinal barrier has been linked to many diseases, like inflammatory bowel disease, asthma and food allergies, but this study provides fresh evidence that GC-C plays a role in the integrity of the intestine.  Strengthening it, the team says, could potentially protect people against inflammation and cancer in the rest of the body.

“If the intestinal barrier breaks down, it becomes a portal for stuff in the outside world to leak into the inside world,” said Dr. Waldman. “When these worlds collide, it can cause many diseases, like inflammation and cancer.”

The role of GC-C outside the gut has remained largely elusive. Dr. Waldman and his team have previously shown its role as a tumor suppressor and biomarker that reveals occult metastases in lymph nodes. They’ve used to it better predict cancer risk, and have even shown a possible correlation with obesity.

Reporting in the Journal of Clinical Investigation, Dr. Waldman colleagues found that silencing GC-C affected appetite in mice, disrupting satiation and inducing obesity. Conversely, mice who expressed the hormone receptor knew when to call it quits at mealtime.

However, its role in intestinal barrier integrity, inflammation, and cancer outside the intestine is new territory in the field.

A new drug containing GC-C is now on the verge of hitting the market, but its intended prescribed purpose is to treat constipation.

This study helps lays the groundwork, Dr. Waldman said, for future pre-clinical and clinical studies investigating GC-C’s abilities beyond those treatments in humans, including prevention and treatment of inflammatory bowel disease and cancer.

“We’ve shown that when you pull away GC-C in animals, you disrupt the intestinal barrier, putting them at risk for getting inflammatory bowel disease and cancer.  And when you treat them with hormones that activate GC-C it helps strengthen the integrity of the intestinal barrier,” Dr. Waldman said.  “Now, if you want to prevent inflammation or cancer in humans, then we need to start thinking about feeding people hormones that activate GC-C to tighten up the barrier.”



Jefferson’s Kimmel Cancer Center Establishes Center to Eliminate Cancer Disparities

Dr. Edith Mitchell, director of newly-established Center to Eliminate Cancer Disparities, and Robin Evans, a patient.

PHILADELPHIA—In an effort to reduce and eventually eliminate cancer disparities among adults in the Philadelphia region, the Kimmel Cancer Center at Jefferson has established the Center to Eliminate Cancer Disparities.

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, will serve as its Director.

Despite the decline in cancer incidence and mortality rates in the United States, disparities in cancer burdens continue to exist among certain population groups and the gap continues to widen.  The Philadelphia region in particular has a disproportionately high number of residents suffering from cancers, many of which are preventable and treatable.

Such disparities include differences in incidence, prevalence, mortality and burden of cancer and related adverse health conditions. Disparate population groups may be characterized by gender, age, race and ethnicity, income, social class, disability, geographic location or sexual orientation.

“I have dedicated my career to the treatment of cancer patients and have had the opportunity to experience, as a physician and as a researcher, the significance cancer disparities can have on the outcome of a patient’s treatment,” said Dr. Mitchell. “The first step in the elimination of these disparities is to raise awareness through public and professional education about what resources are available to groups in their fight against cancer.”

The Center aims to accomplish its mission through the facilitation of disparities-focused research, researcher and clinician education, training and teaching, and increased patient access to quality supportive services, such as palliative care, cancer screening and prevention, and survivorship programs.

Dr. Mitchell and her fellow clinicians and researchers at Jefferson are dedicated to the ongoing study of cancer and other health disparities among patients of diverse ethnic and socioeconomic backgrounds. They have created strategic priorities for eliminating such disparities through innovative research, education and training, advocacy, community outreach, and quality medical care.

The need for research into cancer, and other health care disparities, has become increasingly evident in recent years as doctors and scientists learn more about how slight variations in genetic makeup can have drastic effects on the way cancer invades an individual’s body.  Knowing that these disparities exist can improve how screening processes are established and help doctors understand which treatments will and will not be effective.

Dr. Mitchell has spent her medical career helping individuals in medically underserved areas to realize that simple changes in lifestyle can have a dramatic impact on cancer care. Through her work, Dr. Mitchell has demonstrated the importance of community service and outreach especially to those individuals who may not have the means to seek out more conventional medical advice.

She holds board certifications in both Internal Medicine and Medical Oncology and is a Fellow in the American College of Physicians. She has also served as the Program Leader in gastrointestinal oncology for more than 15 years and has a focused research effort in aggressive breast cancers.

“We want all researchers and clinicians to be aware of the disparities that exist in cancer diagnoses among diverse ethnic groups so that they can incorporate these important factors into their research efforts and clinical practice,” said Dr. Mitchell.

“The Center will also provide patients with contact information for cancer advocacy and support groups both locally and nationally that serve the needs of their demographic background. We are proud to host and sponsor several annual events where patients can come together to share their stories and plan for a future free of cancer disparities,” she said.



Taxpayers Give Back for Cancer: Jefferson Researcher Awarded ‘Refunds for Research’ Grant

Takemi Tanaka, Ph.D., of Thomas Jefferson University’s School of Pharmacy and the Kimmel Cancer Center

Takemi Tanaka, Ph.D., of Thomas Jefferson University’s School of Pharmacy and the Kimmel Cancer Center, received a $50,000 grant toward her breast cancer research, as part of the Pennsylvania Breast Cancer Coalition’s (PBCC) “Refunds for Breast and Cervical Cancer Research” initiative.

The PBCC’s grants are made possible through contributions from state taxpayers who choose to contribute all or part of their state income tax refund to the program.

Dr. Tanaka’s research focuses on breast cancer metastasis. When cancer metastasizes, cancer cells enter the distal organs through the blood vessels. Dr. Tanaka envisions those vessels as a gateway for the cells and wants to close it as tight as possible to prevent the cancer from spreading further.

Her team developed a new drug called ESTA to block the entry of breast cancer cells into the tissue.  Early data show that mice treated with the drug had 60 percent less metastases without toxicity.

From the left: Ashiwel Undieh, Chair of Pharmaceutical Sciences, Pat Halpin-Murphy, founder of PBCC, Dr. Tanaka, and Rebecca Finley, Dean of the Jefferson School of Pharmacy

“I would like to express my sincere gratitude to the tax payers for their generous support for my breast cancer research to help eradicate this deadly disease,” Dr. Tanaka said. “We believe that success with our strategy may transform current breast cancer therapy and move us one step closer to a cure.”

Dr. Tanaka is one of three researchers who received funding through PBCC’s Breast and Cervical Cancer Research initiative. The other recipients are from the University of Pennsylvania and Penn State Hershey Cancer Institute.

“We’re extremely proud of Dr. Tanaka’s recognition by the Pa. Breast Cancer Coalition and thankful for the people in Pennsylvania who donated to help support these grants, as well as the PBCC for their efforts to raise awareness about breast cancer,” said Rebecca Finley, PharmD, M.S., Dean of Jefferson’s School of Pharmacy. “Dr. Tanaka’s work with this promising new drug will only help us better understand and potentially better treat this important health issue in women.”

The PBCC kicked off its annual Refunds for Breast and Cervical Cancer Research campaign to fund the cancer researchers on Monday, Feb. 13 at City Hall with Councilmen Dennis O’Brien.

Since 1997, more than $2.8 million has been donated to the Refunds for Research campaign and 71 grants have been awarded to Pennsylvania researchers looking for the cause of and cure for these common cancers in women.



Curry spice component may help slow prostate tumor growth

Karen Knudsen, PhD, a Professor of Cancer Biology, Urology and Radiation Oncology

Curcumin, an active component of the Indian curry spice turmeric, may help slow down tumor growth in castration-resistant prostate cancer patients on androgen deprivation therapy (ADT), a study from researchers at Jefferson’s Kimmel Cancer Center suggests.

Reporting in a recent issue of Cancer Research, Karen Knudsen, Ph.D., a Professor of Cancer Biology, Urology and Radiation Oncology at Thomas Jefferson University, Supriya Shah, a Jefferson graduate student in Cancer Biology, and colleagues observed in a pre-clinical study that curcumin suppresses two known nuclear receptor activators, p300 and CBP (or CREB1-binding protein), which have been shown to work against ADT.

ADT aims to inhibit the androgen receptor—an important male hormone in the development and progression of prostate cancer—in patients. But a major mechanism of therapeutic failure and progression to advanced disease is inappropriate reactivation of this receptor. Sophisticated tumor cells, with the help of p300 and CBP, sometimes bypass the therapy.

Thus, development of novel targets that act in concert with the therapy would be of benefit to patients with castration-resistant prostate cancer.

For the study, prostate cancer cells were subjected to hormone deprivation in the presence and absence of curcumin with “physiologically attainable’ doses. (Previous studies, which found similar results, included doses that were not realistic.)

Curcumin augments the results of ADT, and reduced cell number compared to ADT alone, the researchers found. Moreover, the spice was found to be a potent inhibitor of both cell cycle and survival in prostate cancer cells.

To help support their findings, the researchers also investigated curcumin in mice, which were castrated to mimic ADT. They were randomized into two cohorts: curcumin and control. Tumor growth and mass were significantly reduced in the mice with curcumin, the researchers report.

These data demonstrate for the first time that curcumin not only hampers the transition of ADT-sensitive disease to castration-resistance, but is also effective in blocking the growth of established castrate-resistant prostate tumors.

“This study sets the stage for further development of curcumin as a novel agent to target androgen receptor signaling,” said Dr. Knudsen. “It also has implications beyond prostate cancer since p300 and CBP are important in other malignancies, like breast cancer. In tumors where these play an important function, curcumin may prove to be a promising therapeutic agent.”



2011 Men’s Event Benefiting Prostate Cancer Research and patient care at Jefferson’s Kimmel Cancer Center

On Tuesday, November, 17th 2011, the Kimmel Cancer Center at Jefferson held the Third Annual Men’s Event benefiting prostate cancer research and patient care at the Prime Rib Restaurant in Philadelphia. The Men’s Event was emceed by Philadelphia Eagles Longsnapper, motivational speaker and magician, Jon Dorenbos.

Receiving the Symbol of Courage was John Beuhler, prostate cancer survivor and grateful patient of Thomas Jefferson University Hospital.  The Symbol of Caring was presented to Kenneth Boone, board member of Thomas Jefferson University Hospital.

Special guests included Amber-Joi Watkins, Miss USA Pennsylvania and Julianna White, Miss USA New Jersey. Guests enjoyed a dinner, silent and live auction, and casino.

The Lead Sponsor was Bill Frankel of Frankel Enterprises. Kimmel Cancer Center would also like to thank the following sponsors:

Sponsor Company / Group Silent Auction/ Company
AP Executive Management Algar Ferrari of Philadelphia
Barry Bressler, Esq. and Betty Gross Eisenberg American Male Salon
BlankRome Annie-Prue
Boone Properties, LLC Atlantic City Country Club
Chamber Orchestra of Philadelphia Bistrot La Minette
Charles Pike Construction Blackfish Restaurant
Citi Blue Horizons Dive Center
Commonwealth Agency, Inc. Boyds
Dann, Dorfman, Herrell & Skillman, PC Chadds Ford
David Yurman Jewelers Chelsea Hotel
DBA The Wyndon Group City of Philadelphia Mural Arts Program
Deitz & Watson Cooperage Wine and Whiskey Bar
Department of Medical Oncology Cross Winds Flight School
Dilworth Paxson D’Angelo’s Restaurant
Drs. Gomella and Family David Yurman
Electronic Ink Dock’s Oyster House/Knife & Fork Atlantic City
Firstrust Drexel University Men’s Basketball
Frankel Enterprises Electronic Ink
Heffler, Radetich & Saitta Fencing Academy of Philadelphia
Hi Fi House Fogo de Chao
Koegle Family Four Seasons Hotel
M&T Bank Kenneth Freeling and Sue Cimbricz
McCullough Models From My Harp – Cheryl Kripke Cohen
PREIT Gomella Family
Rodin IFC Henry A. Davidsen
Stradley Ronon Hidden Creek Golf Club
TD Bank Holt’s Cigar Company
Unique Products Hortman Aviation Services
US Bank J. Lohr
Jacques Ferber
Joseph Anthony Spa
Jump NEA
Kramer Portraits New York
La Prairie
Lacoste
Lacroix
Le Castagne
Lehigh Valley
Limoncello
Lord & Taylor, Bala Cywyd
Lucky Strikes
Manito Equestrian Center
May’s Landing Golf Club
McCullough’s Emerald Golf Links
Merion Country Club
Mid-Atlantic Restaurant
Milkboy
Monsu
Nangellini
Nicole Miller
Pennsylvania Paragliding
Philadelphia Sports Club
Piper Memorial Airport
Quaker State Light Sport Flight Academy, LLC.
Ralph Lauren
Ristorante Panorama
Saks Fifth Avenue, Bala Cynwyd
Salon Ziza
Segway Tours
Skirmish
St. Joe’s University Men’s Basketball
Target Masters Gold Membership
The Chamber Orchestra of Philadelphia
The Little Tuna
The Prime Rib
The Union Trust
The Vesper Club
Thomas J Duffy, Esq.
Tiffany’s
Time Restaurant
Twin Pines Stables and Unique Industries
Twisted Tail
Ultimate Shave
Union League of Philadelphia
Villanova University Men’s Basketball
Villanova University Football
Victory Brewing Co.
Vintage Wine Bar
West Avenue Grille
Whitewater Challengers




The Third Annual Men’s Event would not have been possible without the tremendous work and support of our Committee members:

Barry Bressler Rose Cunningham
Robert DeBolt Marc Feller
Marc Franzoni Peter Gistelinck
Bruce Goldman Tricia Gomella
Niels Haun Mark Juliano
Erik Knudsen Bryan Koegel
John LeVine Bill McCullough
Meredith Seigle Roger Vander Klock
Thomas Walls



Special thanks to Gerard Tomko Wedding Photography for donating his services in-kind.



Jefferson appoints Administrator, Radiation Oncology

Thomas Jefferson University Hospital has selected Alex Khariton to become its Administrator for the Department of Radiation Oncology.

Previously, Mr. Khariton had been the Administrative Director for the Department of Radiation Oncology at Cooper University Hospital in Camden, N.J., for the past eight years.

“I”m looking forward to working for an  NCI-designated cancer center that provides excellent clinical car, partakes in innovative research, and has a well-respected medical school,” says Alex.

Alex is also Co-Chair of the Reimbursement and Economic committee for the SROA (Society of Radiation Oncology Administrators) and a member of  the American Society for Therapeutic Radiology and Oncology (ASTRO).

The new hire announcement was featured online in the Philadelphia Business Journal’s “People on the Move” section:

http://www.bizjournals.com/philadelphia/potmsearch/detail/submission/511141



Drugs targeting chromosomal instability may fight a particular breast cancer subtype

Richard Pestell, M.D., Ph.D, Director of the KCC

Another layer in breast cancer genetics has been peeled back.

A team of researchers at Jefferson’s Kimmel Cancer Center (KCC) led by Richard G. Pestell, M.D., PhD., FACP, Director of the KCC and Chair of the Department of Cancer Biology, have shown in a study published online Feb. 6 in the Journal of Clinical Investigation that the oncogene cyclin D1 may promote a genetic breakdown known as chromosomal instability (CIN). CIN is a known, yet poorly understood culprit in tumor progression.

The researchers used various in vitro and in vivo model systems to show that elevated levels of cyclin D1 promotes CIN and correlate with CIN in the luminal B breast cancer subtype. Cyclin D1 protein is elevated in breast, prostate, lung and gastrointestinal malignancies.

The findings suggest that shifting towards drugs targeting CIN may improve outcomes for patients diagnosed with luminal B subtype. Luminal B breast cancer has high proliferation rates and is considered a high grade malignancy.

Estrogen or progesterone receptor positive and HER2 positive cancers indicate luminal B, and about 10 percent of patients are diagnosed with it every year, though many do not respond well to treatment. The identification of CIN in luminal B provides a new therapeutic opportunity for these patients.

“Cyclin D1 has a well defined role in cell proliferation through promoting DNA replication,” says Dr. Pestell. “My team was the first to discover that cyclin D1 also has alternate functions, which include regulating gene transcription at the level of DNA. We were interested in discovering the function of DNA associated cyclin D1.”

To help answer this, the researchers, including lead author Mathew C. Casimiro, Ph.D., of the Department of Cancer Biology at Thomas Jefferson University, first needed to directly access cyclin D1′s role in gene regulation.

They applied an analysis known as ChIP sequencing to study the protein’s interactions with genes that comprise the entire mouse genome, and found it occupied the regulatory region of genes governing chromosomal stability with high incidence.

They went on to show cyclin D1 promoted aneuploidy and chromosomal rearrangements typically found in cancers.

Faulty chromosomes—either too many or too few, or even ones that are the wrong shape or size—have been shown to be the crux of many cancers. However, a major question of cancer genetics is the mechanisms of CIN. What causes the breakdown in chromosomal stability?

As cyclin D1 expression is increased in the early phases of tumorigenesis, cyclin D1 may be an important inducer of CIN in tumors.

To analyze the association between CIN and cyclin D1 expression in the context of breast cancer, the team aligned an expression of a 70-gene set with the highest CIN score against over 2,000 breast cancer samples. They stratified the samples based on previously described subtypes and aligned them with cyclin D1 expression profiled across the dataset.

A significant correlation among CIN, cyclin D1 and the luminal B subtype was identified, and it was apparent that the relationship between these levels was subtype specific.

“Interestingly, previous studies have presented contradictory results,” Dr. Pestell says. “Many studies have suggested a positive correlation between cyclin D1 expression and outcomes, while others have shown reduced survival. Here, we’ve dug deep, using a genome-wide analysis, and found that overexpression of the protein appears to be directly associated with the genes involved in CIN and this correlates with the luminal B subtype.”

Drugs targeting chromosomal instability for cancer therapy have been explored, but a sub-stratification rationale for the luminal B subtype has not been established. The research presented in this study suggests such a target is worthy of further investigation.

“There is a big drive towards using targeting therapies for stratified breast cancers,” says Dr. Casimiro. “What we are thinking is that there are a growing number of drugs that target aneuploidy, like AICAR and 17-AAG, that may be used as an adjuvant therapy in patients with luminal B breast cancer.”



‘A Welcome New Addition’ to Field: Dr. Juan Palazzo Authors Breast Pathology Book

Juan P. Palazzo, M.D., an anatomic/surgical pathologist at Thomas Jefferson University Hospital and the Jefferson Breast Care Center, has authored a book that tackles the hard cases in breast disease pathology faced by many clinicians in the healthcare world today.

According to Amazon, Difficult Diagnoses in Breast Pathology (Demos Medical) provides a highly visual presentation of the major problems and questions that a pathologist is likely to encounter in the evaluation of common and uncommon breast diseases.

Addressing real-world diagnostic problems faced in daily practice, the book includes needle core biopsy interpretation, diagnosis of precursor lesions, early stage disease, and recognition of neoplastic mimics and other misleading variants.

Each chapter is authored by a recognizePathologist Dr. Juan P. Palazzod expert in the area, and includes hundreds of high-quality images.

“This is a welcome new addition to this field and it delivers with concise, clear writing, ample illustrations, and appropriate comments on ancillary techniques. This latest addition to the field of histomorphology of (surgical) breast disease compares favorably with many more extensive books,” writes Doody’s Reviews.

Dr. Palazzo is pathologist with over 25 years experience and has been named a U.S. News & World Report “Top Doctor.”

The book is available here.



Brachytherapy reduced death rates in high-risk prostate cancer patients, study finds

Xinglei Shen, M.D., a resident in Jefferson’s Department of Radiation Oncology and a part-time master’s degree student in the Jefferson School of Population Health

Brachytherapy for high-risk prostate cancers patients has historically been considered a less effective modality, but a new study from radiation oncologists at the Kimmel Cancer Center at Jefferson suggests otherwise. A population-based analysis looking at almost 13,000 cases revealed that men who received brachytherapy alone or in combination with external beam radiation therapy (EBRT) had significantly reduced mortality rates.

Their findings are reported online January 23 in the International Journal of Radiation Oncology,Biology,Physics.

Brachytherapy involves the precise placement of radiation sources directly at the site of a tumor and is typically used to treat low and intermediate risk prostate cancers. However, brachytherapy treatment for high-risk patients is less common and controversial, given in part to early retrospective studies that found it to be associated with lower cure rates compared to EBRT.

Many experts believe that these early series were limited by poor brachytherapy technique, and that high-quality contemporary brachytherapy may be an effective tool against high-risk prostate cancer.

“The study contradicts traditional policies of using brachytherapy in just low and intermediate risk patients by suggesting there may instead be an improvement in prostate cancer survival for high-risk patients,” said co-author Timothy Showalter, M.D., assistant professor in the Department of Radiation Oncology at Thomas Jefferson University Hospital, and associate research member of Jefferson’s Kimmel Cancer Center. “Although studies like this cannot prove an advantage for brachytherapy, our report does suggest that brachytherapy is no less effective than EBRT and should be considered for some men with high-risk prostate cancer.”

Researchers identified 12,745 Surveillance, Epidemiology and End Results database patients diagnosed from 1988 to 2002 with high-grade prostate cancer of poorly differentiated grade and treated with brachytherapy (7.1 percent), EBRT alone (73.5 percent) or brachytherapy plus EBRT (19.1 percent). The team used multivariate models to examine patient and tumor characteristics associated with the likelihood of treatment with each radiation modality and the effect of radiation modality on prostate cancer-specific mortality.

Treatment with brachytherapy alone or brachytherapy in combination with EBRT, the researchers found, was associated with significant reduction in prostate cancer-specific mortality rates compared to EBRT alone.

Significant predictors of use of brachytherapy or brachytherapy plus EBRT were younger age, later year of diagnosis, urban residence and earlier T-stage.

According to the researchers, including lead author Xinglei Shen, M.D., a resident in Jefferson’s Department of Radiation Oncology and a part-time master’s degree student in the Jefferson School of Population Health, the study’s findings provide ample evidence to further study brachytherapy as part of an effective treatment strategy for men with high-grade prostate cancer.

“Today, for the most part, brachytherapy is not being used for these high-risk patients or even recommended,” Dr. Shen said. “But if you look at the biology and theory behind it, it makes sense: you can really give a lot more dose with brachytherapy than with EBRT alone to the prostate. And this presents an opportunity for high-risk patients.”



KCC To Host Melanoma Research Foundation Symposium

Melanoma Research Foundation

http://www.melanoma.org

CURE OM has announced the inaugural Eyes on a Cure: Patient and Caregiver Symposium to be held on June 16th and 17th, 2012.  The meeting will be held one month after the first CURE OM Scientific Meeting (for physicians and researchers) with the goal of bringing the latest news from the ocular melanoma scientific community directly to patients and their loved ones.  Eyes on a Cure will bring patients, caregivers and researchers from around the world together to offer educational sessions, support groups led by oncology social workers, sessions on complementary therapies, as well as informal time for networking.

This first patient and caregiver symposium will be held in Philadelphia at the Kimmel Cancer Center of Thomas Jefferson University.  Confirmed speakers include: Carol Shields, Takami Sato, David Eschelman, Carin Gonsalves, and James Pingpank.

For more information about the symposium go to the MRF Symposium Announcement



High Dose Vitamin C for Advanced Pancreatic Cancer

By Josh Goldstein, The Daily Dose @Jefferson

A small phase I clinical trial at Jefferson University Hospitals of high-dose, intravenous vitamin C in combination with chemotherapy medications show that this treatment is safe and may have promise for patients with advanced pancreatic cancer.

The study published in the open access online journal PLoS ONE tested the use of intravenous ascorbic acid (vitamin C) three times a week over an eight week cycle in nine patients with metastatic stage IV pancreatic cancer in addition to standard gemcitabine and erlotinib chemotherapy regimens.

“These initial safety data do not reveal increased toxicity with the addition of ascorbic acid to gemcitabine and erlotinib in pancreatic cancer patients,” wrote the team of researchers from the Kimmel Cancer Center at Jefferson as well as the National Institutes of Health (NIH). “This combination with the observed response to treatment suggests the need for a phase II study of longer duration.”

The research was conducted at Jefferson by a multidisciplinary team from the Jefferson-Myrna Brind Center of Integrative Medicine, Jefferson’s Department of Medical Oncology, Department of Surgery, Department of Radiology, and National Institute of Diabetes and Digestive and Kidney Diseases of the NIH.

Daniel A. Monti, MD, Executive and Medical Director of the Jefferson-Myrna Brind Center of Integrative Medicine and lead author of the study said, “We are pleased and encouraged by these results.”

Dr. Monti added, “it is a Jefferson priority to study promising therapies for pancreatic cancer. It is crucial to explore anything that might feasibly give these patients an edge. We are now actively enrolling eligible patients into the Phase II trial.”



New Clinical Trial: Cabazitaxel with Radiation and Hormone Therapy May Improve Prostate Cancer Survival

Jefferson’s Kimmel Cancer Center has started a Phase I clinical trial investigating the latest prostate cancer chemotherapy drug to extend survival, Cabazitaxel, in combination with radiation and hormone therapy. This first-of-its-kind multimodality approach could improve disease control and eventually survival for locally advanced prostate cancer patients.

The single-center, open-label, non-randomized Phase I study of weekly Cabazitaxel with concurrent intensity modulated radiation therapy (IMRT) and androgen deprivation therapy will test its safety and the tolerable maximum dosing.

Cabazitaxel was approved in the U.S. for second-line use in advanced hormone-refractory prostate cancer in men in 2010, and has been described as a major advance in chemotherapy for advanced prostate cancer. It extended overall survival by 2.4 months when compared with mitoxantrone in patients who were previously treated with docetaxel. However, a multimodality approach with the drug has never been studied.

“We know the drug is effective in prostate cancer, but there is no study with radiation and hormone therapy yet,” said principal investigator Jianqing Lin, M.D., an assistant professor of medical oncology at Thomas Jefferson University Hospital. “Concurrent radiation may have a better control for localized disease, and better long-term survival for these high-risk patients.”

IMRT is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor; androgen deprivation therapy is a treatment to suppress or block the production or action of male hormones. Enrolled men will receive weekly treatments of the chemotherapy drug and hormone therapy and then every three months until two years after completion of IMRT.

For the clinical trial, Dr. Lin is partnering with co-investigator Timothy Showalter, M.D., an assistant professor in the Department of Radiation Oncology at Thomas Jefferson University Hospital.

For further information, please contact the Kimmel Cancer Center at Jefferson’s Clinical Research Management Office at 215-955-1661.



KCC’s Brain Tumor Center’s New Immunotherapy Clinical Trial Featured in Several News Outlets

Led by Dr. David Andrews, co-director of the Brain Tumor Center of the Kimmel Cancer Center, a new immunotherapy clinical trial at Jefferson will harvest cells from brain tumors for use in treatment.

In an interview with KYW Newsradio, Dr. Andrews explains that the first step of the trial will be a surgical procedure to take cells from the brain tumor. He adds, ”We then take the tumor cells and treat them with a drug that will induce cell death. The drug itself actually interacts with the immune system.”

Afterwards, the cells are placed in the stomach to work with the immune system to attack the malignant tumor.

Learn more by reading “In Battle Against Cancer, New Trial Fights Fire with Fire“ from KYW Newsradio and ”Immunotherapy Tested on Brain Tumors” from the Philadelphia Tribune.

Information about this upcoming trial was also mentioned on CBS 3.