A National Cancer Institute-designated Comprehensive Cancer Center

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Medical Oncology and Therapeutics Research

Department of Medical Oncology and Therapeutics Research
The Department of Medical Oncology and Therapeutics Research at City of Hope is involved in the diagnosis, treatment, genetic counseling, and research of adult solid tumors. It is also closely aligned with the City of Hope Comprehensive Cancer Center's Developmental Cancer Therapeutics Program.
 
The Department currently includes twenty-one faculty physicians, nine nurse practitioners and physician assistants, five protocol nurse coordinators as well as many basic science faculty. In addition, there is a community practice affiliate of the Department located in Pasadena, California, 15 miles from City of Hope. This practice consists of three full time medical oncologists as well as chemotherapy and protocol nurses. Clinical trials available to City of Hope patients are also available to patients at the Pasadena affiliate site.
 
Clinical
The clinical activities of the Department are organized along the lines of an inpatient hospital service and solid tumor program outpatient clinics. All hospitalized medical oncology patients are admitted to a Medical Oncology Ward Service consisting of an attending faculty member, a fellow trainee, and a physician extender.It has set the standard for the rest of the hospitalin providing well-coordinated inpatient care with continuity and efficiency. The outpatient clinics are organized by solid tumor types with dedicated faculty, protocol nurses and extenders of each solid tumor program caring for patients within specialty clinics. Clinics also include the multidisciplinary involvement of surgeons and radiation oncologists.
 
The Department's commitment to the highest level of oncologic care is reflected in its active participation within the National Comprehensive Cancer Network, an association of NCI-designated Comprehensive Cancer Centers for which City of Hope was one of the founding members. Faculty physicians serve as members of cancer treatment guideline panels for various tumor types. In turn, these panels are responsible for creating nationally accepted algorithms for evidence-based treatment and surveillance of cancer. The guidelines have become accepted as standards by consumers and insurers and represent the cutting-edge therapy available at NCI Comprehensive Cancer Centers typified by City of Hope. Members of the Department are also involved in the teaching of fellows within our highly competitive subspecialtyMedical Oncology and Hematology Fellowship program.
 
Research
Over 30 years ago, the Department of Medical Oncology and Therapeutics Research spearheaded solid tumor clinical research and new drug development. The Department has played a pivotal role within the Phase I and Phase II California Cancer Consortium, a cooperative group funded by the NCIs Cancer Treatment and Evaluation Program (CTEP). This is a consortium of four cancer NCI Cancer Comprehensive Cancer Centers (City of Hope, University of Southern California Norris Cancer Center, University of California-Davis Cancer Center, and most recently University of Pittsburgh). City of Hope serves as the biostatistical coordinating center as well as the pharmacology core facility of this large consortium. Research efforts within the Departmentalso include clinical trials under the aegis of other national cooperative groups including the Organ Dysfunction Working Group (also funded by CTEP), the Cytokine Working Group, Sarcoma Alliance for Research through Collaboration (SARC), as well as Southwest Oncology Group (SWOG), Gynecologic Oncology Group (GOG), Radiation Therapy Oncology Group (RTOG), and National Surgical Adjuvant Breast Program (NSABP).

 

 

Division of Clinical and Molecular Pharmacology

Current therapeutic options for the majority of advanced cancers remain inadequate, highlighting the need for discovery of new anticancer agents directed against novel targets. The mission of the Division of Clinical and Molecular Pharmacology is to investigate the effectiveness of cancer chemotherapeutic agents in order to develop novel molecular-targeted cancer therapies.
 
We study drug mechanisms in DNA damage and repair, signal transduction and DNA synthesis. In addition, we seek to understand mechanisms of drug resistance. Understanding these mechanisms allows us to design more effective drugs. We continue to expand our clinical research in pharmacokinetic, pharmacodynamic and, more recently, pharmacogenomics studies of investigational drugs, which enable us to obtain a clear picture of how these drugs impact the patient. The division aims to bridge the gap between the development of promising new drugs and their application in the clinic.
 
Molecular Pharmacology
Molecular pharmacology uses sophisticated techniques such as computer modeling to identify novel therapeutic targets, e.g., receptors, in cancer. This enables our researchers to design new compounds as well as screen leading drug candidates, such as natural products, from our drug screening program that fit the mechanism of action dictated by the specified molecular target. This process is called target validation.

Clinical Pharmacology
Once target molecules are identified and promising drug candidates are selected, it is crucial to understand the clinical pharmacology of the compounds, that is, how they behave in actual patients. Key research areas within Clinical Pharmacology include pharmacokinetics (the study of drug disposition), pharmacodynamics (drug effects) and pharmacogenomics - the study of genetically inherited determinants of drug response and toxicity.
 
Translational Research
Translational research involves conducting pre-clinical studies on experimental drug therapies and post-clinical analyses on clinical samples. Laboratory-based investigations examine at the molecular level the mechanisms of action and resistance of anticancer agents, including both novel and traditional chemotherapeutic drugs, immunotherapeutics and combinations of anticancer agents and antibodies. The lab helps to facilitate communication between scientists and clinicians studying molecular genetic responses of cells to potential therapeutic compounds, as well as to identify and/or develop biomarkers for targeted therapy.
 

Clinical Trials

The Departmentof Medical Oncology and Therapeutics Research sponsors a large number of therapeutic clinical trials for solid tumor malignancies. These include:
 
  • Phase III trials, which are large comparative studies that most frequently assess survival and progression-free survival
  • Phase II trials, which are smaller studies early in the development of a drug or regimen that typically focus on response and toxicity data
  • Phase I trials, where the primary aim is to determine the types of toxicities and maximum tolerated dose (MTD) of a new agent

View our searchable Clinical Trials Online database for more information.

The Departmentof Medical Oncology and Therapeutics Research is also affiliated with the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Southwest Oncology Group (SWOG) and the Radiation Therapy Oncology Group (RTOG).

For information about enrolling in a clinical trial, contact our New Patient Services department at 800-826-HOPE (4673).

 

 

Professional Education Opportunities

We offer three professional education opportunities.

Medical Oncology and Hematology Fellowship: The Department of Medical Oncology and Therapeutics Research and the Department of Hematology and Hematopoietic Cell Transplantation has provided a three-year fellowship training program in Medical Oncology and Hematology subspecialties for over 25 years. This fellowship is accredited by the national Accreditation Council for Graduate Medical Education (ACGME).

Clinical Oncology Career Development (K-12) Training: In addition, there is a NCI-supported Clinical Oncology Career Development (K-12) Training Program for oncologists at the assistant professor level. The K-12 Program is intended to provide selected trainees a research career development experience in all phases of cancer therapeutic clinical trials. Novel investigator-initiated clinical trials are developed from trainees' basic research projects.

Cancer Genetics Career Development Program: The Division of Clinical Cancer Genetics offers an NIH-fundedprogram thatprovides comprehensive, multi-faceted interdisciplinary training in the genetics of cancer, cancer risk assessment, counseling and risk management, and clinical cancer control and epidemiological research to highly qualified physicians, and doctoral level nurses, to contribute to the pool of program leaders in cancer genetics and cancer prevention and control research.

Research

The research efforts of the Department of Medical Oncology & Therapeutics Research contribute immensely to the progress of the Developmental Cancer Therapeutics Program of City of Hope. This multidisciplinary program spans basic, translational and clinical research by fostering close collaborations among researchers. The overarching long-term goal of the Developmental Cancer Therapeutics Program is to develop more effective and less toxic treatments for cancer. The scientific agenda of the department focuses on the development of novel therapeutic agents for all histologic types of cancer. Faculty members of the department have assumed leadership in bringing innovative cancer therapies in the clinic by designing investigator-initiated, hypothesis-driven clinical trials complementing the industry partners cancer drug development activities. The department's clinical research endeavors are largely responsible for the high patient accrual to the overall cancer center therapeutic trials.

Highlights of Current Efforts
The phase I and phase II California Cancer Consortium (CCC) programs (U01 and N01 grants), funded by the National Cancer Institute Cancer Treatment Evaluation Program, utilizes the combined expertise of City of Hope, University of Southern California and University of California, Davis in the areas of molecular pharmacology, pharmacokinetics, pharmacodynamics, pharmacogenomics, signal transduction, cell cycle regulation, non-invasive imaging and bioinformatics to conduct innovative, laboratory-directed phase I developmental and pharmacokinetic studies that focus on:
  1. agents that target genetic or epigenetic abnormalities in cancer cells;
  2. agents that target signal transduction pathways, the cell cycle and host/tumor interactions;
  3. agents that are potentially active in hematologic malignancies;
  4. agents developed through CCC investigator-initiated RAID projects;
  5. examination of special patient populations for the clinical pharmacology of targeted anticancer agents whose therapeutic effects may be altered because of abnormal organ function or because of inherited differences in genes controlling drug disposition and activity;
  6. identification of new and informative laboratory correlates of biologic activity and drug resistance and exploration of novel functional endpoints of tumor response, progression, and clinical benefit for patients entered on the phase I clinical trials of the CCC.
Principal investigators: Edward Newman, Ph.D., and Robert Morgan., M.D.

The City of Hope  Clinical Oncology Research Career Development Program , a National Cancer Institute K12 Training Program, aims to develop a new generation of clinical oncologic investigators capable of translating basic advances in cancer biology into novel strategies for the diagnosis, therapy and prevention of malignant disease. This multidisciplinary effort will be available to outstanding surgeons, radiation oncologists, pathologists, pediatricians, and internists who have completed their fellowship training in oncology no more than three years previously, and who are appropriate for appointment to the faculty of City of Hope. The curriculum of the City of Hope K-12 Training Program involves both didactic and hands-on experience in basic science, laboratory research, biostatistics and clinical investigation.

Clinical research through the Southwest Oncology Group cooperative grant continues to be an important part of the Departments research portfolio. Faculty members of the department have a long-standing commitment to this cooperative grant as demonstrated by their leadership in the group, involvement in protocol development, meeting attendance and enrollment of patients that exceeds the national annual baseline on clinical trials. (Principal investigator:Joanne Mortimer, M.D.)

Specialized programs integrating basic and clinical research that will establish the best pattern of care for cancer patients aged 65 are the focus of the Cancer and Aging Research Program . Efforts include developing an assessment tool that improves oncologists ability to anticipate chemotherapy toxicity, predicting overall outcomes and developing interventions to improve outcomes among older patients. (Principal investigator: Arti Hurria, M.D.)

Studies in our laboratory revealed that of several vegetable extracts tested, mushroom extract, particularly from Agaricus bisporus, or the common white button mushroom, contain phytochemicals that suppress estrogen biosynthesis via aromatase inhibition. The first clinical trial to test the aromatase inhibition capability of mushrooms in human subjects is now under way in postmenopausal breast cancer survivors. (Principal investigator: Melanie Palomares, M.D., M.S.)

Several multi-institutional studies on assessing biomarkers associated with targeted therapy in nonsmall cell lung carcinoma focused on the expression of several human tissue kallikreins, a family of 15 secreted serine proteases, are now currently accruing patients. (Principal investigator:Karen Reckamp, M.D., M.S.)

Our basic science collaborators have evaluated the effect of an extract of white button mushroom on prostate cancer cell lines in vitro and vivo. We determined that mushroom extract significantly inhibits cell proliferation in a dose-dependent manner in all cell lines tested. Taken together with research from other laboratories, our results support the concept of testing white button mushroom as a dietary component that may aid in the treatment of asymptomatic men with biochemical recurrence of prostate cancer. (Principal investigator: Przemyslaw Twardowski, M.D.)

Despite recent advances in molecularly targeted therapies for cancer, primary brain tumors, particularly high-grade gliomas, remain a serious clinical challenge for oncologists. A major obstacle to successful pharmacologic treatment of central nervous system tumors is the blood-brain barrier (BBB), which prevents most anticancer agents from entering the central nervous system. Another key reason for the lack of success in treating gliomas is their diffuse and highly infiltrative nature; no clear border exists between tumor and normal brain. Glioma cells disseminate from the primary site, forming microtumor foci throughout the brain that often hide behind an intact BBB. To make a significant impact on the survival of brain tumor patients, new therapies must not only be able to navigate through or around the BBB, but they should also specifically target the invasive tumor cells that escape currently available treatments. The effectiveness of gene therapy has been limited by the inability of the carrier cells to deliver therapeutic agents with sufficient distribution throughout primary and distant tumor sites. Human neural stem cells (NSCs) hold great promise for glioma therapy due to their inherent tumor-tropic properties. They can track to infiltrative tumor cells and localize to distant microtumor foci. When modified to express a therapeutic transgene, NSCs can serve as vehicles for drug delivery, in effect circumventing the BBB to deliver a concentrated amount of active drug directly to tumor cells while minimizing toxicity to normal brain tissue. (Principal investigator: Jana Portnow, M.D.)

Liposarcomas are the second most common soft-tissue sarcoma. The use of HIV protease inhibitors is associated with the HIV protease-induced lipodystrophy syndrome. This syndrome is characterized by peripheral fat wasting, central fat accumulation, insulin resistance and hyperlipidemia. Preclinical studies suggested alteration of sterol regulatory element binding protein-1 a lipogenic transcription factor, in the development of this syndrome. Based on the biology of this syndrome and its proposed pathophysiology, we hypothesized that HIV protease inhibitors might serve as novel, targeted agents against liposarcoma. As a result of these preclinical studies, we have developed a Food and Drug Administration-funded clinical trial of nelfinavir for recurrent liposarcomas. (Principal investigator: Warren Chow, M.D.)

New Developments
Strategic, integrated programs on Intracerebral Microdialysis in Rats Bearing Orthotopic Glioma and Treated with Genetically-modified Neural Stem Cells: The central hypothesis of this pilot study by collaborators from the Developmental Cancer Therapeutics Program and the  Hematologic Malignancies (HM) Program of City of Hope, and with combined expertise in intracerebral microdialysis, pharmacology and NSCs, is that NSC-mediated expression of high levels of CE will convert CPT-11 to SN-38 extracellularly and that the SN-38 will diffuse into adjacent invasive brain tumor cells and eradicate them. Our objective within this proposal is to use intracerebral microdialysis to assess whether SN-38 is produced in vivo in the area of tumor after intracranial delivery of NSCs and systemic administration of CPT-11. (Principal investigators: Jana Portnow, M.D., Karen Aboody, M.D., and Timothy Synold, Pharm.D.)

Preclinical studies on renal cell carcinoma (RCC) therapeutics are under way in collaboration within the laboratories of Eleanor Hua Yu, Ph.D., and Stephen J. Forman, M.D. STAT3 has been identified as a downstream target of Sunitinib and shown that Sunitinib directly induces RCC apoptosis and growth arrest in a STAT3 dependent manner. These findings will have impact on the future design of new strategies on the use of Sunitinib for RCC patients.
 

Medical Oncology Team

Support This Program

It takes the help of a lot of caring people to make hope a reality for our patients.  City of Hope was founded by individuals’ philanthropic efforts 100 years ago. Their efforts – and those of our supporters today -- have built the foundation for the care we provide and the research we conduct. It enables City of Hope to strive for new breakthroughs and better therapies – helping more people enjoy longer, better lives.

For more information on supporting this specific program, please contact our  Donor Relations Department at 800-667-5310 or developmentrelations@coh.org. Or, to make a gift that supports all the research at City of Hope,  donate online now . We thank you for your support.
 
 
 
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