The scientific agenda of the Division of Medical Oncology has changed substantially over the past four years, with an increased emphasis on translational research based on fundamental concepts of molecular biology. This approach has been predicated on the emerging knowledge of the molecular correlates of anticancer drug resistance, increased understanding of the genes associated with familial and sporadic patterns of malignancy (colorectal and breast cancer, in particular), the immunological basis of tumor response and resistance, and a more precise assessment of the pharmacology of novel anticancer compounds. In this
way, the Division has become even more central to the translational research program of the USC/Norris Comprehensive Cancer
Center.

An increased focus of interaction with scientists of the USC/Norris Comprehensive Cancer Center has been developed, leading to several interdisciplinary projects that have allowed overlap of several of the scientific programs of the center - Genitourinary, Gastrointestinal, Breast Cancer, Developmental Therapeutics and several core programs. Our list of publications attests to the level of interdisciplinary collaboration that has been achieved, with detailed reports of preclinical assessment of new anticancer compounds, pharmacology of anticancer agents, molecular mechanisms of resistance to fluoropyrimidine and other cytotoxic agents, and genes associated with breast, genitourinary and colon cancer. Members of the Division have also assumed a leadership role in a key NIH-funded multicenter trial assessing molecular correlates and utility of adjuvant chemotherapy for invasive bladder cancer.

Members of the Division have assumed leadership roles in the scientific agenda of the Southwest Oncology Group, with emphasis on cancers of the genitourinary tract, breast, gastrointestinal tract, bronchus and skin, and have provided core laboratory resources for translational trials conducted by the Southwest Oncology Group and the Cancer and Acute Leukemia Group B. Important leadership, clinical and scientific, has been provided to the Phase I-II Consortium, funded by the National Cancer Institute, shared between City of Hope National Medical Center, University of California-Davis and USC. Extensions of this work in the Division of Oncology has led to an important collaboration with the staff of the Children's Hospital of Los Angeles in the development of several novel anticancer agents, with an emphasis on retinoid biology in cancer therapeutics.

In a key development, members of the Division have led the USC program of immunotherapeutic research in cancer, with the development of tumor antibodies as therapeutic tools, and the use of novel cytokines administered by inhalational routes. Of particular importance has been the study of vaccines for patients with malignant melanoma and with cervical cancer, as well as the utility of bispecific antibodies directed against determinants on prostate cancer.

Faculty Research Areas

John Daniels, M.D.
Chemobolization of Liver Tumors
Breast Cancer Prevention

Agustin A. Garcia, M.D.
Gynecological Oncology
Gastrointestinal Tumors
Breast Cancer Treatment

Syma Iqbal, M.D.
Gastrointestinal Tumors, including Esophageal Cancer, Gastric Carcinoma, Metastatic Gallbladder and Colon Cancers

Raymond A. Kempf, M.D.
Immunobiology of Renal Cell Carcinoma and Malignant Melanoma
Limb Salvage Chemotherapy of Bone and Soft Tissue Sarcoma
Phase I and Phase II Studies of Biological Response Modifiers

Heinz J. Lenz, M.D.
Molecular Tumor Profiling to Predict Outcome
Regulation of Gene Expression Involved in Drug Resistance (TS, TP, ERCC1, GST-P1, XPD)
Germline Polymorphisms as Predictors of Clinical Outcome and toxicity
Development of Novel Agents and Identification of Novel Targets

Jacek K. Pinski, M.D., Ph.D.
Prostate Cancer
Clinical Trials in Hormone Refractory Prostate Cancer

David I. Quinn, M.D., Ph.D.
Clinical and Molecular Predictors of Cancer Outcome
Molecular Cancer Profiling for New Therapeutic Targets
Development of New Anticancer Therapies - Phase I/II Trials and Molecular Correlates

Christy A. Russell, M.D.
Systemic Treatment of Breast Cancer

Darcy V. Spicer, M.D.
Breast Cancer Treatment and Prevention

Jeffrey S. Weber, M.D., Ph.D.
Translational Immunotherapy in Melanoma
Bispecific Antibody for HER2/neu with Prostate Cancer
Antigen Peptide Pulsed Dendritic Cells for Metastatic Melanoma

Special Basic Research Activities

Jacek K. Pinski, M.D., Ph.D.
This prostate cancer cell biology laboratory investigates the effects of the bone microenvironment on proliferation, invasiveness, differentiation, and apoptosis of prostate cancer cells. New in vitro and in vivo models for studying the interactions between prostate cancer cells, osteoblasts, stromal cells, and neuroendocrine cells are being developed. The mechanisms of action, and potential therapeutic applications of paracrine factors, which are released by cells of the prostate cancer microenvironment and are involved in the process of transdifferentiation of cancer cells, are being investigated. For example, we have shown that the cytokine, interleukine-6, which is released in significant amounts from osteoblasts, can significantly inhibit the growth prostate cancer xenografts in mice by the process of neuroendocrine transdifferentiation. We have also documented that the proliferation of prostate cancer cells is markedly suppressed when these cells are co-cultured in the presence of terminally differentiated neuroendocrine cells. Further investigations are focused on studies analyzing these observations.