Director's Message: Outlook for 2014

Dear Members of the Case Comprehensive Cancer Center community:

I am writing to congratulate you on an incredibly successful 2013 and a remarkable outlook as we begin 2014. As you all are aware, our outstanding rating from our 2012 NCI review has received national attention. The combined research and clinical trials efforts, the coordination of interdisciplinary collaborative research, and efforts we make in research across institutions all gained recognition and respect.

Of course, none of us can rest on our laurels. Luckily, we have had many scientific advancements and grant successes in a very restrictive environment, and have recruited outstanding faculty to join our campuses to help us further our cancer research mission. I would like to provide just a few examples of each of these accomplishments.

Research Highlights

Jarek Maciejewski published a series of articles in Nature Genetics on the genetic abnormalities in AML and MDS. Working with a strong team of investigators, he has shown the importance of SETBP1, and the spliceosome gene U2AF1. As a result, the team is now continuing their investigation of AML and developing a unique gene set for diagnosis and prognosis in AML and MDS.

John Wang and his collaborators within the GI SPORE published an article in Cancer Cell describing the role of p110 alpha from the catalytic subunit of PIK3CA that alters the function of mutant cells driving proliferation, leading John to propose a target for drug discovery.

Mark Griswold published a groundbreaking analysis of magnetic resonance fingerprinting as a novel method for interpreting MRI signals in patient scans. His Nature publication outlined a new approach that may provide a rapid and more integrated simultaneous noninvasive quantitation of multiple important properties of tissues, in particular brain tumors. It is not an overestimation to say that this could become transformative to tumor imaging.

Jeremy Rich and members of the brain tumor SPORE in development are evaluating the fundamental biology of brain tumors. Some of the investigators are working on brain tumor initiating cells, while others are publishing in areas of vasculogenesis, drug resistance, and genomic correlates of disease progression.

David Wald published in Leukemia on the importance of targeting glycogen synthase kinase three (GSK3) as a target for differentiation therapy in AML. Based on his studies, a phase 1 trial with GSK3 inhibitors is currently ongoing.

Greg Tochtrop is pursuing, with John Letterio, the synthesis of novel triterpenoids as anti-inflammatory agents and chemopreventives for individuals at high risk for cancer.

Cheryl Thompson and Li Li have been collaborating on a number of projects evaluating the importance of red meat carcinogens and the risk for colon cancer, the role of sleep in breast cancer phenotype and the genetic variations, and 15 -prostaglandin dehydrogenase and colon cancer susceptibility (PLOS1).

Scientific Programs

In the programmatic area, the Cancer Center consolidated our basic sciences into one main program, even as many laboratories provide the scientific base to our other scientific programs. We initiated a new Breast Cancer Program led by Lyndsay Harris and Bill Schiemann. Other transitions in leadership in 2013 include the appointment of Yogen Saunthararajah as co-leader of the Developmental Therapeutics Program, taking over for the now retired Ernie Borden.

Clinical Trials

Our clinical trials accrual, through the effort of over 80 physicians who accrue patients and over 130 staff, reached a record for the Center of 1008 patients entered into therapeutic clinical protocols. Many thousands participate in intervention, genomics and screening trials. We have accruals across all disease types, an accomplishment that is unusual for all but the top few NCI-designated centers.

Recruitment

We have recruited a number of outstanding investigators to the Center. These include:

Leadership

  • Jame Abraham, MD: Director, Breast Oncology [Cleveland Clinic]
  • Jonathan Haines, PhD: Director, Institute for Computational Biology and Chair, Epidemiology and Biostatistics [CWRU/UH]
  • Alok Khorana, MD: Sondra and Stephen Hardis Chair in Oncology and Vice-Chair for Clinical Services, and Director, Gastrointestinal Malignancies Program [Cleveland Clinic]
  • Navneet Majhail, MD: Director, Bone Marrow Transplant Program [Cleveland Clinic]
  • Johannes Wolff, MD: Chair, Pediatric Hematology Oncology and Blood and Marrow Transplantation [Cleveland Clinic]
  • Anthony Wynshaw-Boris, MD, PhD: Chair, Genetics and Genome Sciences [CWRU/UH]
  • Qing Yi, MD, PhD: Chair, Cancer Biology [Cleveland Clinic]

Additional Recruits

  • Mohammed Abazeed, MD, PhD: Drug discovery and development; radiation biology [Cleveland Clinic]
  • Stefanie Avril, MD: Breast cancer pathology [CWRU/UH]
  • Jennifer Carew, PhD: AML Drug development [Cleveland Clinic]
  • Hetty Carraway, MD: Experimental therapeutics of acute leukemias [Cleveland Clinic]
  • Yan Feng, MD, PhD: Lung cancer clinical research [CWRU/UH]
  • Aaron Gerds, MD, MS: Transplant and non-transplant therapies for disorders of bone marrow failure, in particular the myelodysplastic syndromes and myeloproliferative neoplasms [Cleveland Clinic]
  • Michael Gibson, MD: Head and neck cancer developmental therapeutics [CWRU/UH]
  • Betty Hamilton, MD: Hematopoietic stem cell transplantation for myeloid malignancies and novel strategies for the prevention and treatment of graft versus host disease [Cleveland Clinic]
  • Christopher Hoimes, MD: GU Clinical research [CWRU/UH]
  • Huiping Liu, MD, PhD: Genomics of breast cancer stem cells [CWRU/UH]
  • Anant Madabhushi, PhD: Complex microimaging and merger of large databases in diagnosis [CWRU/UH]
  • Alberto Montero, MD: Development of novel targeted breast cancer therapies [Cleveland Clinic]
  • Sudipto Mukherjee, MD: Leukemias, myelodysplastic syndromes and other bone marrow failure conditions, including clinical trials of new treatments [Cleveland Clinic]
  • Nima Sharifi, MD: Androgen metabolites in prostate cancer [Cleveland Clinic]
  • Vinay Varadan, PhD:Translational bioinformatics involving the integrative analysis of next generation sequencing data derived from patient tumor samples, namely breast cancer and GI malignancies [CWRU/UH]
  • Vamsidhar Velcheti, MD: Treatment of thoracic malignancies with a focus on lung cancer [Cleveland Clinic]
  • Shaveta Vinayak, MD: Breast cancer genomics and risk assessment [CWRU/UH]
 

2014: Shaping up to be a Great Year

As we move forward into 2014 each of these teams will continue their outstanding investigation and many others of you will follow through with groundbreaking observations and publications. With an emphasis on promoting Transdisciplinary Collaboration and Coordination, the Cancer Center will also help efforts in the following initiatives:

Ohio Clinical Trials Collaborative (OCTC)
The OCTC is a part of the Governor of Ohio Medical Corridor Initiative, which is specifically meant to link infrastructure of the three CTSAs in Ohio, leverage infrastructure to highlight the doctors and researchers in Ohio, and promote investigator-initiated therapeutic trials. The other participating CTSAs include Ohio State and the James Comprehensive Cancer Center and University of Cincinnati and the UC Cancer Center. Initiated in October 2013, the goals of the OCTC are to develop cross institution investigator-initiated trials and pharma-sponsored clinical trials. As of January 2014, three clinical trials, two in patients with glioma and one in head and neck cancer, are being considered. This effort is led by Jill Barnholtz-Sloan.

Brain Tumor SPORE Initiative
Jill Barnholtz-Sloan and Steven Rosenfeld lead the initiative of a Brain Tumor SPORE working group within the Basic Sciences Program. This cross-institution collaboration involves investigators from CWRU, UH, Cleveland Clinic, and Nationwide Children's Hospital. Project leaders include: Justin Lathia, Bingcheng Wang, Candece Gladson, Peter Houghton (Nationwide Children's), and Jill Barnholtz-Sloan.

Multidisciplinary Institute for Research on Applied Imaging & Innovation
Mark Griswold of the Cancer Imaging Program has been asked by CWRU President Snyder to lead this new Institute. The goals are to develop a cross-disciplinary effort in imaging for the institution. Prime areas of development will be in cancer imaging, and the underlying premise is that coordinating input in clinical, therapeutic, and genomic imaging will facilitate concept development and application.

High Throughput Screening Initiative
The School of Medicine is coordinating development of a high throughput screening core facility with the help of the Departments of Genetics and Pharmacology, Cancer Center, and Taussig Cancer Institute. Using support allocated to the Cancer Center in the CCSG renewal, the institute will purchase the PE Operetta imaging system, drug libraries, shRNA library, and related robotic systems that enable high throughput drug screening using both molecular and whole cell systems.

Drug Development - Institutional Support
In 2013, the Cancer Center recognized the need to amass cross-institutional commitment to support member drug development efforts. I am happy to say we have done so. At CWRU, the Council to Advance Human Health has been assembled to provide investigators with advice, venture and seed capital, and commercial links to develop drugs in CWRU laboratories. This has benefited Susann Brady-Kalnay, Clark Distelhorst, Sandy Markowitz, Elma Baron, Kevin Cooper, and Bingcheng Wang. At UH, the Harrington Project has developed a national competition to promote physician-scientist development of new drugs. Of the 20 awards to date, Cancer Center members Sandy Markowitz, David Wald and Goutham Narla were named as Harrington Scholars, providing them with research funding and advice on commercial development. Likewise, at Cleveland Clinic Innovations, Yogen Saunthararajah and Ernie Borden are receiving support for drug development efforts. In addition, the Translational Research and Pharmacology Core Facility is providing early preclinical assessment of drug efficacy in tumor cell lines and animal PK, and the Athymic Animal and Xenograft Core Facility is developing patient derived xenografts (PDX) for drug screening.

We enter 2014 as a highly interactive center with numerous exciting and leading-edge research efforts. I look forward to working with all of you.

Stanton L. Gerson, MD
Director, Case Comprehensive Cancer Center
slg5@case.edu