MESSAGE FROM THE DIRECTOR
Stan Gerson, MD
Director, Case CCC
I would like to update the membership on a number of initiatives that have recently taken place in the Cancer Center. Each of these changes was discussed at our recent External Advisory Board meeting and each met with their approval.
Developmental Therapeutics Program
Yogen Saunthararajah has assumed the position of co-Program Leader of the Developmental Therapeutics Program with Afshin Dowlati. Yogen is a Professor of Medicine at CCLCM and Associate Staff in the Department of Hematologic Oncology and Blood Disorders at the Cleveland Clinic. He is active in drug development, having successfully brought combination oral THU-decitabine, for more effective in vivo non-cytotoxic epigenetic-differentiation therapy of malignant and benign diseases, through the NIH RAID program. This combination drug is now in clinical trials. Combining oral decitabine with an inhibitor of cytidine deaminase, the enzyme which rapidly inactivates cytidine analogue drugs, facilitates epigenetic treatment goals by extending the Tmax of decitabine for S-phase dependent DNMT1-depletion without the high Cmax that causes off-target anti-metabolite effects and cytotoxicity. This combination drug also enables decitabine pharmacologic activity in cytidine deaminase rich organs such as the liver (a sanctuary site for cancer cells from cytidine analogue treatment effects), an important consideration in treating cancer.
Yogen will work with program members to facilitate the identification of lead compounds in drug discovery for investigators with a novel molecular target. He will also advise on drug development through preclinical in vivo models that phenocopy human disease, a crucial step needed to attract NIH or venture capital support for IND-enabling studies, which has emerged as a major institutional interest and strength. Coordinating these efforts in the Cancer Center will allow us to continue to be at the forefront of innovative drug development for cancer applications.
I wish to thank Ernie Borden for his leadership of the Developmental Therapeutics Program. He will continue to be a member of the Developmental Therapeutics Program and will contribute to the melanoma research efforts, the development of phosphatase inhibitors, and will advise members on clinical trials applications. Ernie also continues as editor of Seminars in Oncology.
Basic Science Consolidation
As we continue to evolve the focus of our scientific programs in the Cancer Center, we decided to consolidate our basic science programs into a single Basic Sciences Program (final name to be determined) and a new Breast Cancer Program. This reorganization reflects the mission of the Cancer Center to promote scientific discovery towards disease-based research and evaluation in preclinical and clinical research settings, which ultimately lead to changes in patient care. A close interface between basic science discoveries and disease-based impact reflects a dynamic tension between discovery and application.
Clark Distelhorst and Alex Almason lead the new consolidated Basic Sciences Program, which consists of 41 members across the institutions. After a retreat this past month, they established three focus areas that will provide members with areas of potential interest and collaboration:
- Cell Death, led by Shigemi Matsuyama
- DNA Damage Response, led by Junran Zhang
- Signaling and Microenvironment, led by Danny Manor
Each focus area will meet to plan collaborative efforts and present scientific progress by members, and the entire program will meet monthly with presentations by one of the focus groups.
Two strong translational initiatives cut across this new program. One in lymphoid malignancies and focused on CLL, is studying the biology, DNA repair, and bcl2 processes that characterize this disease and which may be exploited in new therapeutic approaches. The other is the brain tumor group, led by Steve Rosenfeld and Jill Barnholtz-Sloan, which is preparing a SPORE application with projects in angiogenesis, drug resistance, and genomic markers of prognosis.
As a result of the consolidation of programs, Susann Brady-Kalnay and George Stark have stepped down from their roles as program leaders. George remains active on the Executive Committee and will be a strong voice for basic research in the Cancer Center. Susann is actively pursuing her research into imaging altered phosphatase function in glioma and other tumors as a means to identify tumor migration and metastasis. Her work is a shining example of translation from discovery to potential clinical application. I want to thank them both for their exceptional leadership of the Cancer Cell Signaling Program for many years.
Breast Cancer Program
The new Breast Cancer Program, led by Lyndsay Harris and Bill Schiemann, has collected our breast cancer research community of clinical, translational and basic scientists into one program. This new structure will assist our efforts to bring an understanding of the basis processes of breast cancer development, recurrence, and metastasis, and link them to better tools for prognosis and treatment. The program will include a strong basic biology into the etiology of breast cancer, prominent genomics initiative, studies of EMT, and an initiative in high risk assessments for families of breast cancer patients. The recruitment of more than 11 investigators to our institutions in the past five years has enabled us to develop this program.
The 34 members have identified four focus areas to pursue collaborative efforts:
- TME & Metastasis, led by Bill Schiemann
- Transcription & Gene Regulation, led by Hung-Ying Kao
- Mammary Gland Development & Transformation, led byMark Jackson
- Population Sciences, led by Cheryl Thompson
Each of these areas will benefit from clinical research application both from population and tissue-based studies as well as novel investigator-initiated therapeutic clinical trials. Recent accomplishments highlight the trajectory of this new program:
- Development of a breast cancer tissue microarray (TMA)
- Completion of a large population-based screening/ mammographic density trial with TMA and blood samples
- Identification of a cohort with CNS metastasis (matched primary and mets)
- Database of triple negative breast cancer with a repository with clinical and race annotation
- Gene Expression data from over 400 primary breast tumors with clinical annotation including treatment
- Piloting of a Multidisciplinary Genomics Tumor Board for Breast Cancer
This is an exciting time of transition for our Center. Please contact myself or your program leader if you have any questions.
CASE CCC IN THE NEWS
Case Western Reserve School of Medicine Wins Prestigious NCI Sponsored Provocative Questions Grant
Newswise - Oct 14, 2013
The National Cancer Institute's (NCI) new Provocative Questions research funding program has awarded a prestigious grant to researchers at the Case Comprehensive Cancer Center and Case Western Reserve University's Schools of Medicine and Engineering to study tumor detection at the earliest stages of growth. "We know that the best way to fight cancer is to find tumors when they are small and have not yet left their primary location," said principal investigator Susann Brady-Kalnay, PhD, Professor of molecular biology and microbiology and member of the Case Comprehensive Cancer Center at Case Western Reserve University..."Dr. Brady-Kalnay's novel approach is built on her discovery of an abnormal protein fragment on tumor cells that encourages their movement through tissue," statedStanton Gerson, MD, Asa and Patricia Shiverick- Jane Shiverick (Tripp) Professor of Hematological Oncology, director of the Case Comprehensive Cancer Center and director of the Seidman Cancer Center at UH Case Medical Center...In addition to Brady-Kalnay, the research team includes Mark Griswold, PhD, professor of radiology; Vikas Gulani, MD, PhD, Assistant Professor of radiology; Zheng-Rong Lu, PhD, the M. Frank and Margaret Domiter Rudy Professor of Biomedical Engineering; and David Wilson, PhD, the Robert J. Herbold Professor, Biomedical Engineering.
Clinical Research Brochure for African Americans
The Case CCC Minority Accrual Committee (MAC) is pleased to announce the publication of a Clinical Research Brochure for African Americans. This brochure was developed by MAC members to open and facilitate a dialogue with African American patients and their families about clinical research. The brochure is available electronically at on the Clinical Research Office website. Hard copies of the brochure can be requested from Katarzyna Karelus, Case CCC Clinical Research Office, firstname.lastname@example.org or 216.844.4176.
MARK YOUR CALENDARS
Graft-versus-Host Disease (GvHD) National Symposium
Registration today the Graft-versus-Host Disease (GvHD) National Symposium, Friday, November 1 at the Embassy Suites Cleveland. This conference is intended to raise awareness about the signs and symptoms of GvHD, review cutting edge approaches to prevention and treatment, and highlight and promote research to further our understanding of its cause. The symposium will have two tracks: a scientifically rigorous one for physicians and practitioners, and a survivor track that will focus on challenges faced by BMT recipients and their families. CME credit is available.
Conquer Cancer Foundation of the America Society of Clinical Oncology
Conquer Cancer Foundation of the America Society of Clinical Oncology (ASCO) is accepting applications for the following funding opportunities:
- The Conquer Cancer Foundation of ASCO Medical Student Rotation for Underrepresented Populations is a funding opportunity designed to facilitate the recruitment and retention of individuals from populations underrepresented in medicine to cancer careers and increase access to quality care for underserved communities. To qualify, applicants must be enrolled in an MD or DO, U.S. medical school program and be of an underrepresented population as defined by the program eligibility criteria. Candidates must be U.S. citizens, U.S. nationals, or permanent residents. Candidates also must demonstrate an interest in pursuing oncology as a career and have a record of good academic standing.
Deadline: December 17
- The Conquer Cancer Foundation of ASCO Resident Travel Award for Underrepresented Populations (RTA) is designed to facilitate the recruitment and retention of individuals from underrepresented populations in medicine to cancer careers and increase access to quality care for underserved communities. To qualify, applicants must be enrolled in an ACGME-accredited residency program required for future training in a cancer related subspecialty (i.e. Internal Medicine considering Med/Onc, Surgery considering Surg/Onc) and be of an underrepresented population as defined by the program eligibility criteria. Candidates must be U.S. citizens, U.S. nationals or permanent residents. Candidates must demonstrate an interest in pursuing oncology as a career as well as a record of good academic standing.
Deadline: December 17