From radiological techniques in cancer diagnosis and therapy to stem cell biology, researchers at the Siteman Cancer Center are closing in on important advances in cancer care and prevention. Siteman’s seven formal research programs are listed below.
Breast Cancer Research
The long-term goals of the Breast Cancer Research Program (BCRP) are to elucidate the basic mechanisms that regulate breast cancer pathology and to use this information to develop strategies for prevention, diagnosis and treatment of all stages and subtypes of breast cancer. Working groups in clinical, basic and population sciences have been established to identify and develop novel strategies for implementation in the diagnosis and treatment of breast cancer. These three groups work in collaboration guided by the hypothesis that advances in basic and population science can be leveraged to have a unique clinical impact in successfully treating breast cancer. These institutional translational efforts are categorized in three specific aims:
- To expand clinical treatment of breast cancer using research-based paradigms.
- To utilize institutional expertise in basic sciences to identify new translational targets and treatment regimens and help advance these clinically.
- To reduce risk and ethnic disparities in breast cancer through targeted prevention and genomic strategies.
BCRP includes 23 faculty members from eight departments and three schools across Washington University and Saint Louis University campuses to form an integrated group dedicated to research on the prevention, diagnosis and treatment of breast cancer. Program members have diverse interests, including:
- Breast health communications
- The pathology and biology of premalignant lesions
- The development of intrinsic breast cancer subtype assays
- Translational research on endocrine therapy resistance in the context of cooperative group neoadjuvant endocrine therapy trials
- The development of novel therapeutics that target both tumor cells and bone and immune system cells
We also are very actively investigating novel imaging approaches for predicting response to hormonal therapy. In addition, the program is collaborating with Washington University’s Genome Center in an effort to unravel the genetic changes associated with breast cancer susceptibility, initiation, progression, relapse and resistance. Program members are advancing new breast cancer models in order to develop preclinical justifications for investigator-initiated clinical trials in our developmental therapeutics programs. Classes of agents under development include phosphoinositol-3-kinase inhibitors, hedgehog inhibitors, check point homolog kinase (CHK1) inhibitors and Trop2 antibodies.
Hematopoietic Development and Malignancy
The Hematopoietic Development and Malignancy Program (HDMP) includes 29 Washington University faculty members from four departments. The long-term goals of the HDMP are to elucidate basic mechanisms regulating normal and malignant hematopoiesis and use this information to develop strategies for the prevention, diagnosis, prognostic stratification and treatment of hematopoietic malignancies. We have identified areas of institutional strength and developed the following specific translational goals:
- To leverage local expertise in cancer genomics to identify key genetic and epigenetic alterations in hematopoietic malignancies and develop their translational potential
- To Develop fundamental discoveries in immunology into novel immunotherapies for hematopoietic malignancies
- To translate fundamental discoveries in stem cell biology into novel strategies to treat hematopoietic malignancies and/or improve stem cell transplantation
- To expand translational research in multiple myeloma and lymphoma
Groups in leukemia, lymphoma & myeloma, myelodysplastic syndrome and transplantation biology have been established to develop, review, prioritize and conduct translational research. The HDMP fosters collaborative translational research and provides training of junior investigators through research seminars, journal clubs, work-in-progress meetings and the annual HDMP retreat.
Washington University has a long history of research in the area of imaging. Investigations on the clinical application of the first computed tomography scanner were carried out at Washington University, and positron emission tomography was initially developed here. The Oncologic Imaging Program at Siteman Cancer Center has 41 members from seven departments and three schools. The major goals of the OIP are to facilitate new research initiatives, expand ongoing collaborations, train students and fellows, support junior faculty, and develop new methods to address fundamental and clinical cancer imaging needs. These goals will be accomplished through intra- and inter-programmatic activities and external partnerships.
The program’s highest priorities include developing imaging agents and technologies for detecting, diagnosing and treating cancer, as well as increasing the understanding of animal models utilized in basic cancer research. OIP activities will be guided by the following specific aims:
- Develop new novel imaging instruments for diagnostic applications and image-guided cancer therapies
- Develop novel molecular imaging agents for accurate detection, assessment of tumor-specific properties, and monitoring therapeutic response to improve treatment outcomes
- Elucidate the molecular mechanisms of cancer therapy by developing novel preclinical molecular imaging models and methods to understand tumor biology and enhance therapy
- Educate, train, and mentor students, fellows, junior faculty and the community in cancer imaging research
Prevention and Control
The Prevention and Control Program includes 35 members from nine different departments and three schools: Washington University School of Medicine, Washington University School of Social Work and Saint Louis University School of Public Health. The program’s overarching goal is to develop and conduct research across the cancer continuum that is transdisciplinary in nature and translational in focus.
Within the program, transdisciplinary research spans from cell to society to address key problems in cancer prevention and control, including disparities, tobacco control, energy balance and genetics. Translational research evaluates efforts to implement and disseminate evidence-based cancer control initiatives into clinical and public health practice as well as health policy. To achieve these goals, the Prevention and Control Program:
- Provides scientific leadership that identifies and actively promotes opportunities for transdisciplinary and translational cancer prevention and control science
- Recruits and supports new scientific talent with interests and experience in transdisciplinary and translational areas
- Assembles and supports transdisciplinary teams across Siteman Cancer Center
- Coordinates seminars, workshops and training sessions that help shape the research concepts and skills of cancer prevention and control conducted by researchers
- Builds community partnerships to assure Siteman Cancer Center’s research is responsive to local community needs, NCI Objectives and is accountable for timely translation of research into practice
Leading-edge transdisciplinary and translational research is underway across the program. Examples include studies examining and reducing breast cancer disparities, improving tobacco control, energy balance and maximizing the benefits of cancer genetics research for cancer prevention.
Fifteen years ago, a strategic decision was made to promote basic science research in tumor immunology and establish an infrastructure to facilitate clinical translation of cancer immunotherapies at Siteman Cancer Center (SCC) through the creation of a Tumor Immunology Program (TIP) as an integral component of a newly-forming NCI-designated Comprehensive Cancer Center. This strategic decision has proved to be prescient, and today the number of laboratories at SCC performing tumor immunology-related research has increased significantly. In the last five years there has been an increase in the number of laboratories performing translational tumor immunology research and a number of investigator-initiated cancer clinical trials are ongoing. This increase in translational research has been achieved through the creation of an environment where interactions between basic scientists and physician scientists occur easily and often and where state-of-the-art resources are available to facilitate translation of basic science research findings into novel therapeutic opportunities. As a result of the environment that was established by the SCC, the highly interactive nature of the basic immunology research community now extends to the work being performed in the areas of tumor immunology and cancer immunotherapy. Efforts of Tumor Immunology Program members are currently focused into four central themes: (1) the dynamic interplay between the immune system and cancer, (2) the molecular basis of immune recognition of cancer, (3) the impact of inflammation and immunosuppression on cancer development and (4) cancer immunotherapy.
The long-range goal of the Tumor Immunology Program is to encourage the development of cutting-edge basic science research in tumor immunology and facilitate the direct translation of basic science insights into novel therapeutic opportunities. Toward these ends, the following four immediate goals will be pursued:
- Develop new experimental mouse models that precisely recapitulate the dynamic interplay between the human immune system and developing tumors in cancer patients
- Identify tumor-specific molecules that serve as targets of innate and adaptive immune responses and explore mechanisms to enhance the recognition of these molecules as a platform for novel immunotherapies
- Define the role of inflammation and/or regulatory elements of the innate and adaptive immune system in either promoting or suppressing antitumor immune responses
- Translate basic immunologic research into clinically relevant tests and interventions
The program will achieve these goals by continuing to sponsor a number of interactive scientific forums for its members and their research teams and by employing the resources of the Siteman Cancer Center and its shared resources to encourage the active and interactive participation of both its basic and clinically oriented members. The Tumor Immunology Research Program currently consists of 34 members from five departments in the School of Medicine.
Solid Tumor Therapeutics Program
The Solid Tumor Therapeutics Program (STTP) of the Siteman Cancer Center consists of 58 members representing 14 departments across the Washington University School of Medicine and Saint Louis University campuses, provides training of investigators at all levels of experience and offers educational opportunities, including seminars, courses, retreats, journal clubs, workshops and work-in-progress meetings.
The overall goals of STTP are to apply discoveries in ‘omics and DNA repair research to novel clinical trials for solid malignancies, especially endometrial, gastrointestinal, non-small cell lung, astroglial and prostate cancers. The approaches in different disease site cancers are linked by common approaches and shared group applications. Developmental Therapeutics provides the expertise and capability for early phase trials for this purpose. Investigators are also integrally involved in research aimed at translating their studies to the clinic in several ways including the identification of small molecule inhibitors of novel DNA damage response pathways that illuminate the causes of cancer or have potential uses in treatment. Inclusion of DNA repair studies in this program is based on 1) the theme that genetic instability and DNA repair defects are key to solid tumor initiation, maintenance and therapy resistance, and 2) discovery of molecules that impair DNA repair that will become available for early phase clinical studies.
Specifically, the program will focus on the following aims:
- Develop and apply state-of-the-art ‘omics technology for solid tumor clinical trials.
- Utilize genomics and imaging to further expand our vibrant Developmental Therapeutics Group.
- Utilize ‘omics for clinical trials in solid tumors in Neuro, Thoracic, Gastrointestinal, Genitourinary, and Gynecologic Oncology.
- Define molecular mechanisms of DNA repair for use in novel clinical trials.
Cell-to-Cell Communications in Cancer
The long-term goal of the new Cell-to-Cell Communications in Cancer Program (C4P) is to unravel the complex cellular communication that occurs between tumor and non-tumor cells that is pivotal to cancer development, progression and metastasis and to work closely with clinicians across all Siteman Cancer Center programs to translate our basic findings to the patient. Membership includes individuals focused on understanding how stromal cells, including non-tumor epithelial cells, adipocytes, immune cells, vascular cells and fibroblasts, and extracellular matrix structural proteins, growth factors and cytokines interact with tumor cells to impact the tumorigenic process. The aims of the program are as follows:
- To identify key communication molecules and pathways (i.e., targets) in tumor-stromal interactions that impact tumor and tumor stromal cell proliferation, survival, adhesion and motility and then to develop strategies to target these key molecules or pathways
- To translate the basic science discoveries of C4P by fostering intra-programatic interactions with clinician-scientists within our program and by bridging inter-programatic interactions between our working groups and translational investigators across all SCC research programs
Each aim is focused on the central importance of communication in the cancer microenvironment. Each member has specific expertise and shared goals that have been and will continue to be utilized to develop a program with strong and fruitful intra-programmatic and inter-programmatic interactions. C4P has 39 members from ten departments and two schools.
C4P is organized around three broad areas that reflect the expertise of membership and hold the potential to translate basic findings to novel therapeutic modalities.
(1) Metastatic Bone Group
The metastasis group primarily focuses on unraveling the molecular mechanisms that impact the metastatic process including how stromal cells impact the pre-metastatic niche and the immune landscape at the metastatic site
(2) Lung Cancer Group
This group focuses on lung cancer development, progression, metastasis and treatment
(3) Brain Cancer Group
The group focuses on brain cancer development, progression and treatment