City of Hope provides a multidisciplinary, interactive environment where basic, clinical and translational, and prevention and control scientists collaborate closely. This stimulating intellectual environment contributes to the productive translational research under way within the Comprehensive Cancer Center. Our research initiatives are divided into the following research programs:
Basic Science Research Program
The Comprehensive Cancer Center provides both the infrastructure and the environment for outstanding basic science research. ("Basic science" refers to research conducted in a laboratory setting.) In turn, this research contributes to our understanding of the underlying genetic, molecular and biological bases of cancer. The basic science research program at City of Hope is called
Molecular Oncology (MONC).
Clinical and Translational Research Programs
The Comprehensive Cancer Center's clinical and translational research programs focus on the translation of novel laboratory observations into the treatment of patients (and their families) and, ultimately, throughout the world. The number of the Center's novel (Phases I and I/II) clinical trials increases yearly. The clinical and translational science research programs are:
Cancer prevention and control research at the Comprehensive Cancer Center is conducted within a program on
Cancer Control and Population Sciences (CCPS).
The members of this research program cover an extensive spectrum of disciplines, which is further broadened by additional collaborations with physician investigators. Such a confederation of expertise, working within a collaborative environment, maximizes productive interaction. The program focuses on four important areas of concentration:
Host and environmental determinants of cancer
Health-related outcomes and quality of life after cancer
Interventional studies to reduce cancer-related morbidity
Our five research programs, described above, represent a continuum, as shown in the figure below. Basic and translational studies can originate in either the basic science program,MO or the DCT Program. These studies can then link to phase I and II clinical protocols in all three clinical programs—DCT, CI and HM. They can also integrate into follow-up studies in survivorship and symptom management in the CCPS Program. On this continuum, CI spans both translational and clinical research, whereas HM is predominantly (but not exclusively) clinical. Frequent interaction between the principal investigators of each program ensures maximum benefit from shared insights. All these activities are made possible by City of Hope’s infrastructure, which supports basic and translational research in biological and in small molecule approaches to cancer.
The arrow in the figure below represents our realization that, even as activities move to the right toward clinical realization, there is a strong requirement to recycle back to developmental activities in response to the knowledge we gain in early clinical application. Our scientists are already doing this routinely, aided by our flexible and responsive infrastructure. The CCPS Program also contributes to the cycle by providing downstream information on effects of therapy and also potential prevention and therapeutic targets — findings arising out of survivorship and molecular epidemiological work of CCPS. These findings may then be explored by other programs in the continuum.
Cancer Control and Population Sciences (CCPS) Program
Smita Bhatia , M.D., M.P.H., Co-leader
Susan L. Neuhausen, Ph.D., Co-leader
Program Members-If you would like an updated membership list, please contact Kim Lu at firstname.lastname@example.org.
The mission of the Cancer Control and Population Sciences (CCPS) Program is to advance the science and application of cancer etiology, prevention and outcomes, and reduce the burden of cancer and its sequelae across all segments of the population through collaborative, multidisciplinary efforts. The CCPS team brings together expertise in these areas, fostering an interactive, cancer-focused research environment. The CCPS mission will be accomplished through the following scientific goals:
Goal 1: To identify host and environmental factors contributing to development of cancer and develop approaches for risk assessment, risk reduction and early detection of cancer
Goal 2: To describe health-related outcomes and quality of life (QOL) in cancer patients
Goal 3: To develop, implement and evaluate interventions to reduce cancer-related morbidity and mortality, and improve QOL from diagnosis and treatment, through survivorship and end-of-life
Goal 4: To understand causes of disparities in cancer risk assessment and outcome, and develop targeted interventions to reduce disparities
Goal 5: To disseminate evidence-based research results through structured educational initiatives
CCPS conducts highly focused, hypothesis-driven and interactive research from etiology, prevention and early detection of cancer through symptom management, cancer survivorship and end-of-life issues. These research activities serve as a platform for interventional and educational initiatives. The Center of Community Alliance for Research & Education(CCARE)facilitates the comprehensive cancer center's ability to provide cancer education to underserved populations. The Center for Cancer Survivorship provides state of the art comprehensive care long-term to cancer survivors, but in the setting of clinical research.
CCPS Members' Research
Members of the CCPS Program represent broad expertise in cancer etiology and prevention, genetic risk assessment, QOL and end-of-life care, outcomes and cancer survivorship. The underlying theme that unifies the CCPS Program is research in a wide range of disciplines related to cancer control and population sciences. Members of this program interface with the basic science, translational and clinical research programs to integrate laboratory and clinical studies with population-based studies.
Peter P. Lee, M.D., Co-leader
Hua Yu, Ph.D., Co-leader
Program Members -If you would like an updated membership list, please contact Kim Lu at email@example.com.
The Cancer Immunotherapeutics (CI) Program is focused on discovery and application to clinical practice of efficacious and minimally toxic immunotherapeutic interventions for cancer. The long-term goal of the CI Program is to develop insights made by tumor immunologists into novel therapeutic approaches in preclinical model systems, which are then taken through rigorous process development to yield therapeutics of sufficient quality for use in human clinical trials.
CI has established a robust support team comprising the regulatory, cGMP manufacturing and clinical trials infrastructure to conduct first-in-human clinical exploration under Food and Drug Administration (FDA)-authorized investigational new drugs (INDs). We established the Clinical Immunobiology Correlative Studies Laboratory for the purpose of generating data from treated patients and, using validated assay platforms, informing our translational and basic scientists of clinically relevant immunobiology that impacts therapeutic efficacy and safety.
CI has three major components: (i) basic tumor immunology, (ii) antibody-based immunotherapeutics and (iii) cell-based immunotherapeutics. Program research spans understanding basic principles of immunologic escape by tumors, engineering of antibodies and antibody fragments for radioimmunotherapy, imaging and the derivation of immunocytokines, use of viral vectors for tumor vaccines and genetic engineering of T cell s for adoptive immunotherapy.
INDs and Clinical Protocols
The CI Program's growing portfolio of active FDA INDs covers a variety of genetic engineering products, recombinant antibody proteins and genetically modified cells.
FDA-authorized clinical protocols cover a growing number of patient populations, including those with CEA-expressing carcinomas (colorectal and breast), prostate cancer, glioma, lymphoma and childhood neuroblastoma.
In the next few years, additional protocols for lung cancer, ovarian cancer, leukemias and pediatric embryonal brain tumors will be added, and multimodality immunotherapy protocols will commence.
Develop and improve lymphocyte genetic engineering and adoptive T cell transfer-based immunotherapy for oncologic disease
Develop molecularly-targeted therapies to overcome tumor-induced immune suppression, thereby enhancing the efficacies of cell- and antibody-based immunotherapeutic modalities
Develop novel antibody-based therapeutics for imaging and treatment of both solid tumors and hematopoietic malignancies
CI Members' Research
Members of the CI Program have expertise in the specialized areas of cancer immunotherapy and tumor immunology. Of particular interest to this program are the fields of antibody-based radioimmunotherapy, cell- and vaccine-based immunotherapeutics, immunopharmacologic drugs, signaling between tumor and immune cells in the tumor microenvironment, tumor-induced immune suppression, and phase I and II clinical trials. Knowledge gained from these studies is applied toward development of innovative, multimodality cancer therapeutics to enhance immune responses against tumor cells.
Karen Aboody, M.D., Co-leader
Edward Newman, Ph.D., Co-leader
Program Members - If you would like an updated membership list, please contact Kim Lu at firstname.lastname@example.org.
The long-term goal of the Developmental Cancer Therapeutics (DCT) Program is to develop more effective and less toxic treatments for cancer. This multidisciplinary program spans basic, translational and clinical research by fostering close collaborations among basic and clinical researchers. While the program continues its long-standing strength in evaluating cancer therapeutics developed by collaborators at other academic institutions and the pharmaceutical industry, the major emphasis of this program moving forward is on the development of novel, molecularly-targeted cancer therapeutics at City of Hope .
Our mission is not to compete with the pharmaceutical industry, but rather to complement cancer drug development and partner with the industry for the ultimate purpose of bringing innovative cancer therapies into the clinic.
Our major focus is on:
(a) unique molecular targets that may not be high priorities for the pharmaceutical industry,
(b) natural products screening and synthesis of natural product derivatives and
(c) matching targeted therapies with appropriate molecular subtypes of tumors.
To identify and validate new molecular targets for innovative cancer therapy approaches
To select and develop novel small-molecule inhibitors of promising molecular targets
To investigate molecular and pharmacologic mechanisms of drug action and drug delivery
To translate basic and preclinical studies into early phase clinical trials for treatment of cancer
DCT Members' Research
Members of the DCT Program have expertise in a wide spectrum of disciplines essential for development of innovative, molecularly-targeted cancer therapeutics. These include molecular target identification by gene expression profiling, target validation by RNAi approaches, lead compound selection by computational and high-throughput screening approaches, total synthesis of natural products and their derivatives, structure-activity relationships, combinatorial chemistry, pharmacokinetics and pharmacodynamics, and phase I and II clinical trials. This broad range of highly-specialized areas of expertise is focused on a concerted effort to develop new cancer therapeutics, from target identification through drug development to clinical trials.
Stephen J. Forman, M.D., Co-leader
Ravi Bhatia, M.D., Co-leader
Program Members - If you would like an updated membership list, please contact Kim Lu at email@example.com.
The long-term goal of the Hematologic Malignancies (HM) Program is to improve outcomes for patients with leukemia, lymphoma, Hodgkin's disease and multiple myeloma. HM integrates basic, translational and clinical research related to the pathogenesis and treatment of hematologic malignancies through close collaborations between basic and clinical researchers. The major areas of focus are to (a) expand opportunities and optimize outcomes for potentially curative treatment with autologous and allogeneic transplantation, (b) increase understanding of malignant stem cells in hematologic malignancies to improve cures and c) develop new, nontransplant experimental therapies for hematologic malignancies.
Recently, HM has expanded research in nontransplant therapeutics and leukemia biology. The success of monoclonal antibodies such as Rituxan (rituximab) and Campath (alemtuzumab) in the treatment of chronic lymphocytic leukemia and novel small molecules such as Gleevec (imatinib) in chronic myelogenous leukemia has made this area fertile ground for study.
Clinical and research programs have been established for specific disease entities, including acute and chronic leukemia, Hodgkin’s and non-Hodgkin’s lymphoma, and multiple myeloma. With clinical and basic scientists working together, this creates an expanded repertoire of studies focused on individual diseases, which complements our transplant modality-driven investigations. The HM Program then shares results of these studies with researchers and clinicians in other Cancer Center Programs.
Develop novel autologous and allogeneic transplant regimens to improve safety and efficacy of treatment, and expand their use to underserved populations including patients with HIV and older people with hematologic malignancy.
Study mechanisms regulating normal and malignant hematopoietic stem cells (HSCs), and develop therapies based on manipulating normal HSCs and interventions targeting malignant stem cells.
Develop novel non-transplant therapeutic studies of epigenetic mechanisms, molecular targets of gene expression, RNAi and immune-based treatments.
HM Members' Research
Members of the HM Program design and lead phase I/II clinical trials using novel therapies for hematologic malignancies. The expertise represented by this group includes cytogenetics and molecular diagnostics, pathology, hematopoietic cell transplantation and graft-versus-host disease, gene- and cell-based therapies, stem cell research and biostatistics. Members of this program collaborate closely with other research programs, including Developmental Cancer Therapeutics and Cancer Immunotherapeutics, for development of small molecule- and immunological-based cancer therapeutics.
Emily Wang, Ph.D., Co-leader
Binghui Shen, Ph.D., Co-leader
Program Members -If you would like an updated membership list, please contact Kim Lu at firstname.lastname@example.org.
The overall scientific vision of theMolecularOncologyProgram (MONC)is to investigate fundamental DNA and RNA biology for the purpose of understanding basic mechanisms of cancer and ultimately identifying potential new therapeutic approaches. The major emphasis is on understanding the biology of cancer cells, which is accomplished by investigating the development of cancer, studying the biological mechanisms of cancer development, discovering information on key targets for cancer therapy, and developing advanced technologies used in cancer research.
Investigations into the mechanisms of DNA damage and repair mechanisms form one foundation of this program and are relevant to cancer development. Changes in cellular gene expression that accompany tumor growth are equally important to cancer progression. Studies of DNA methylation and epigenetics represent a second strong component of the program. Investigators studying transcriptional and post-transcriptional mechanisms of gene regulation contribute yet another dimension to this program. Changes in gene expression during cancer cell progression can result in a variety of events that promote uncontrolled cellular growth. These include altered splicing patterns and disregulation of the microRNA population, both of which lead to additional alterations in gene expression. Nuclear receptors and transcription factors have traditionally been important chemotherapeutic targets; theMolecular Oncologyprogram includes a group of investigators studying these important macromolecules and their ligands.
Understand the relationship between DNA damage and repair, mutagenesis, and carcinogenesis at the molecular level.
Investigate the fundamental processes underlying gene regulation, epigenetics and RNA biology during cell lineage commitment and tumor formation.
Members of theMolecular OncologyProgram have expertise in diverse areas of basic cancer biology that include chromatin structure, receptor-mediated control of gene expression, regulation of transcription by tissue- and cell-specific transcription factors, small drug interactions with and modulation of DNA and RNA function, cell signaling mechanisms, regulation of RNA processing, and the use of epigenetic tools such as siRNA and ribozymes to modulate gene expression. These basic science studies provide the foundation for future development of novel approaches to cancer therapy by the DCT, CI and HM Programs.
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