Division of Oncology

Research

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The Division of Oncology increased its 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.

The Division has increased its interaction with scientists at the Cancer Center, which has led to several interdisciplinary projects that have allowed overlap of some of the scientific programs of the Center, including Genitourinary, Gastrointestinal, Breast Cancer, Developmental Therapeutics and several core programs. The division’s list of publications attests to the level of interdisciplinary collaboration that has been achieved, including 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 hold leadership roles in a key NIH-funded multicenter trial assessing molecular correlates and utility of adjuvant chemotherapy for invasive bladder cancer.

Oncology faculty have leadership roles in the scientific agenda of the Southwest Oncology Group (SWOG) and have provided core laboratory resources for translational trials conducted by the Group. In addition, important clinical and scientific leadership has been provided to the Phase I-II Consortium (funded by the National Cancer Institute and shared between City of Hope National Medical Center, University of California, Davis and USC).

Members of the Division have led the USC program of immunotherapeutic research in cancer. Of particular importance has been the study of vaccines for patients with malignant melanoma and cervical cancer, as well as the utility of bispecific antibodies directed against determinants on prostate cancer.

Division of Oncology faculty published 106 peer-reviewed research papers during the January 1 through December 31, 2015 period, and another 15 are in press.

Faculty Research Areas

  • Treatment of Prostate Cancer, Development of Proteomic Technologies, Cancer Biomarker Development, Clinical Trials with Molecular Targeted Therapeutics, Applications of Nanotechnology in Cancer

  • GU Oncology/Lymphoma

  • Treatment of GI Malignancies, Development of Phase I Program for Drug Development in GI Oncology, Design and Conduct of Clinical Trial in GI Oncology

  • Tracking cancer plasticity and resistance using laboratory models and liquid biopsy samples from patients

  • Treatment of Prostate Cancer, Clinical and Laboratory Aspects of Cancer Research, Developmental and Experimental Therapeutics Focused on Prostate Cancer, Molecular Profiling to Identify New Cancer Biomarkers, Androgen Receptor Signaling and Signaling Transduction in Cancer

  • Treatment of Sarcoma/Myeloma

  • Sarcoma, Neuro-Oncology, Testicular Cancer

  • Mass Spectrometry, Proteomics, Elucidation of Novel Clinical Prognostic Markers

  • GI Malignancies, Lung Cancer

  • Treatment of CNS/GI Oncology

  • Treatment of lung, head and neck malignancies, Drug development, Biomarker development, Digital tools in cancer care, Equity in cancer care

  • Treatment of Prostate Cancer, Clinical Trials in Hormone Refractory Prostate Cancer

  • Treatment of GU Malignancies, 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

  • Clinical Biomarker Discovery: “Shotgun” Proteomics, Tumor/Host Modeling, Statistical Analysis of High-Dimensional Biological Data, Experimental Design

  • Treatment of GU Oncology, Cancer Outcomes, Health Economics, Healthcare Policy

  • Breast Cancer Treatment and Prevention, Human Subjects Research

  • Modulating myeloid derived suppressor cell function to alter response to checkpoint inhibition, Accounting for heterogeneity of the suppressive immune microenvironment according to tumor site, Investigation of novel therapeutics targeting immunosuppressive cells, Racial disparities of the immune response in breast cancer. 

    Lab website: https://sites.usc.edu/roussostorreslab/

  • Treatment of Breast Cancer and Leukemia

  • Treatment of Breast Cancer, Clinical Trials and Development of Anticancer Therapies, Novel Biomarkers, Diet and Cancer

  • Identification of novel targets for drug development as well as predictive and prognostic markers, Early drug development in preclinical models, Early Clinical Trials, GI Cancer including Colon Cancer, Stomach Cancer, Pancreas Cancer and Biliary Cancers

  • Treatment of Gastrointestinal malignancies, Cancer Biomarker Development, Development of Novel Therapeutics in GI malignancies
    Healthcare Disparities, Improving Diversity in Clinical Trials

  • Treatment of GI Malignancies, Novel drugs or approaches for the treatment of GI cancers -Esophageal Cancer, Gastric Carcinoma, Hepatobiliary Cancers, Colorectal Cancer, Pancreas Cancer and Neuroendocrine Tumors

  • Treatment of Genitourinary Malignancies, Clinical Trials related to immunotherapy related adverse events and benefit of nephrectomy in metastatic renal cell carcinoma.

Clinical Research

Special Clinical Research Activities

Breast/Women’s Cancers Program

Over the last year, the clinical trials portfolio has grown in number and accrual, with an ongoing focus on investigator-initiated and other trials to translate early findings emanating from USC-generated research and through internal and external collaborators. Progress has also been made in securing grants as well as other funding for clinical trials efforts and outreach. The Program has continued to generate pivotal publications that change research directions and clinical practice.

Accrual has been completed to a study assessing soy effects on breast cancer risk biomarkers (breast density), and results from an earlier green tea prevention study have been published by Dr. Spicer. Drs. Russell and Spicer had their work published in prestigious journals such as Lancet Oncology, Journal of Clinical Oncology, Clinical Cancer Research, Breast Cancer Research and Treatment, The Oncologist, Breast and Frontiers in Oncology.

Genitourinary Cancer Section

The Genitourinary Cancer Section of the Division of Medical Oncology has continued to make meritorious progress in the past year. Members have excelled in obtaining peer reviewed funding, running innovative clinical trials and publishing in high-impact journals.

Dr. David Agus received an R01 grant to explore the potential for modeled therapeutics across different cancers as an extension of work done in the Physical Sciences-Oncology Consortium grant. In addition, his book A Short Guide to a Long Life graced the New York Times bestseller list for a second year in a row. Dr. Amir Goldkorn excelled in his work on circulating tumor cells with publications on CTC numbers and CTC telomerase expression and a new R01 grant with Dr. Jacek Pinski for correlatives for the SWOG trial S1216, which adds the hydrolyze inhibitor orterenol to initial androgen deprivation therapy in metastatic prostate cancer. In an NCI grant-funded phase I/II clinical trial, Dr. Pinski also continued his focus on the LH receptor pathology in prostate and other cancers with development of doxorubicin linked to a LH avid molecule that binds the drug to cancer cells; the work will be published in Clinical Cancer Research. Dr. Mitchell Gross worked on the development of resistance to androgen pathway blockade in prostate cancer with high-technology interrogation of CTCs that demonstrated the phenomena of c-myc amplification and androgen receptor aberration as resistance develops; the work was presented at AACR. Dr. James Hu is the USC Principal Investigator on several internationally important germ cell cancer trials, working through SWOG as well as with the Australian New Zealand Urology and Prostate Cancer Group and Memorial Sloan Kettering Cancer Center. In addition, he continues his physician leadership role with the Adolescent Young Adult program. Dr. David Quinn continues work with eribulin in urothelial cancer, with translational and correlative studies in prostate cancer, genomic-therapeutic combinations and fasting in chemo protection and sensitization. Dr. Sarmad Sadeghi joined the GU team from Cleveland Clinic and received an NCI CTEP Career Development Award for his clinical trial work looking at gemcitabine and eribulin in non-cisplatin eligible patients with advanced urothelial cancer. He will also pursue an interest in outcomes research and modeling of cost contingencies in GU cancer care.

Section members have published in high-impact journals including the New England Journal of Medicine, Lancet Oncology, Journal of Clinical Oncology, Cell Stem Cells, Journal of Nuclear Medicine and Journal of the National Cancer Institute. Future clinical trials will focus on emergent checkpoint inhibitors, mutation targeted agents and EphB4. Key collaborations are ongoing with colleagues in the Departments of Urology, Radiation Oncology, Pathology, Pharmacy, Gerontology, Preventative Medicine, Radiology and Nuclear Medicine as well as with other Cancer Center members.

Basic Science Research

Special Clinical Research Activities

Amir Goldkorn, MD

Dr. Goldkorn’s research program focuses on developing the therapeutic and prognostic potential of circulating tumor cells, cancer stem cells, and telomerase – three areas that offer unique opportunities to better understand and surmount cancer heterogeneity.

  1. Circulating Tumor Cells (CTCs) are cancer cells shed by solid tumors into the bloodstream, where they can be captured and analyzed. Dr. Goldkorn’s team is leading CTC studies in a phase III multi-center prostate cancer trial as well as a multicenter bladder cancer trial. CTC capture and NextGen sequencing is also being conducted in several other clinical trial settings and in mouse models to identify drivers of tumor resistance and disease progression. Dr. Goldkorn also founded and directs a CTC Research Core at USC Norris.
  2. In the area of Cancer Stem Cell (CSC) research, Dr. Goldkorn’s laboratory discovered that cancer cells could cyclically lose and regain CSC properties, a phenotypic plasticity that is mediated in part by PI3K/AKT (upstream) and β-catenin/CBP (downstream). Most recently, gene expression profiling of 300 radical prostatectomy specimens showed that AXIN2, a transcriptional target and feedback regulator of β-catenin, is predictive of cancer recurrence after prostatectomy and directly regulates invasion and tumor formation.
  3. Telomerase is a reverse transcriptase ribonucleoprotein that protects and lengthens telomeres at the ends of chromosomes. Telomerase activation is an essential step in the formation and progression of >90% of all malignancies and therefore may constitute an effective therapeutic target across heterogeneous malignancies. Dr. Goldkorn’s team is currently working to develop a novel therapeutic strategy that interferes with telomerase to preferentially kill cancer cells.

Jacek Pinski, MD, PhD

Dr. Pinski is a tenured Associate Professor of Medicine practicing at the Norris Comprehensive Cancer Center, where he combines clinical care with basic research on the biology of prostate cancer and other hormonal cancers. He completed medical school and earned his PhD in Frankfurt, Germany before coming to the U.S. in 1990, to work at the Tulane University in New Orleans, with Nobel laureate Andrew Schally, MD, one of the pioneers of hormonal therapy in oncology. From 1998 until his move to California in 2001, Dr. Pinski received continued clinical training in Medical Oncology at the Baltimore Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, where he collaborated with John Issacs, PhD, another respected figure in prostate cancer research. His publications comprise more than 100 articles in the field of cancer research and he has been the recipient of multiple awards and grants from the NCI, DOD and ACS. Dr. Pinski’s area of focus has been in studying the role of the hypothalamic/pituitary hormones in cancer and in the value of novel prognostic and predictive molecular markers related to hormonal synthesis for clinical outcomes in cancer patients.

Collaborate Information

For people interest in collaborating with this Division, the research liaison is Darcy Spicer, MD.

  • The first research area is focused on cancer plasticity, based on Dr. Goldkorn’s observations that populations of cancer cells can spontaneously and cyclically shift to and from a drug resistant, tumorigeneic phenotype. He studies the epigenetic, transcriptional, and metabolic switches driving this plasticity, with the ultimate goal of elucidating resistance mechanisms that can be targeted therapeutically.

    Goldkorn’s second area of focus is in the field of liquid biopsies, peripheral blood samples that can be used to analyze circulating tumor cells and cell-free DNA and RNA shed by tumors. He founded and operates an NCI designated Liquid Biopsy Research Core at the USC Norris Comprehensive Cancer Center (first in the nation), where he receives and analyzes thousands of patient blood samples. The ultimate goal of this research is to develop and validate new biomarkers that inform and improve treatment decisions.

  • Immunotherapy in soft tissue sarcomas

    Effects of physician leadership training on organizational outcomes

    Economic effects of cancer on Adolescent Young Adult patients

  • In has a clinical research focus on advanced cutaneous tumors, including melanoma, cutaneous squamous cell carcinoma, basal cell carcinoma, Merkel cell cancer, and cutaneous lymphomas.  Current clinical trials will explore the role of targeted therapies, immunotherapy, and intratumoral therapies for cutaneous malignancies.

    In also has a translational research focus through collaborations with molecular biology, immunology and epigenetics, to explore novel approaches to treating these cancers.

    In’s population-based research in affiliation with epidemiology and preventive medicine, explores disparities in skin cancer, such as those affecting minority groups, adolescent and young adults, and transplant recipients

  • Thomas is principal investigator on several industry supported phase I dose escalation studies or expansion studies, including a novel liposomal gemcitabine agent, a combination trial of cabozantinib plus atezolizumab, and a novel CD8 PET CT imaging study for patients treated with immunotherapy agents as examples.

    Thomas is an integral member of the “Phase I” team and have accrued many patients to early phase clinical trials. His patient data was presented at ASCO 2019 for one of the trials he participated in.

    Thomas obtained the Ming Hsieh Institute grant for the proposal “Pilot feasibility study to evaluate the immunomodulatory effects of FID-007 at two dose levels in patients with solid tumors.” HE will examine the immunomodulatory effects of this novel taxane in order to inform which dose could be most synergistic in combination with an PD-1 targeting antibody.

    Thomas is writing an investigator initiated clinical trial combining sEphB4-HSA with nivolumab as neoadjuvant therapy for patients with high risk resectable melanoma. The trial will have 30 patients with a primary objective to determine the rate of complete pathologic response to treatment. He is collaborating with Parkash Gill to design relevant correlative studies. He is in late talks with an industry sponsor to fund the trial.

    Thomas is collaborating with a small company to obtain tissue from patients with solid tumors responding to checkpoint inhibitor therapy. The goal is to isolate T cells from the tumor specimens and identify the specific T-cell receptor targets in order to design rational T-cell therapies that may be tested in phase I studies in the future.

  • Kang’s research interests lie in early phase clinical trials, breast cancer supportive care and patient experience.

  • The Lenz laboratory oversees a large number of research projects including molecular characterization of a large number of colon cancer samples and blood from a number of randomized phase II and III studies from more than 2500 patients.

    The Lenz laboratory collaborates with Dr. Fariborz Nasertorabi from University Park Campus. They have equipment for isolating CTC and doing RNA seq on CTC.

    The Lenz laboratory has 3-4 international postdoctoral fellows (Japan, Italy and China). Dr. Lenz have a lab manager, lab technician, data manager, Statistican, Bioinformatician, PHD scientist, animal technician in my laboratory

  • Breast cancer clinical trials and correlative biomarkers research.

    Clinical trials with therapeutic and novel agents, such as new immunotherapy agents and studies; PARP inhibitors; CDK 4/6 kinase inhibitors and agents that reverse CDK resistance; new HER2 agents (such as Tucartinib, Margetuximab, Neratinib) and new combinations of HER2 therapies.

    Design and conduct investigator initiated clinical trials in breast cancer.

    Breast cancer CTC liquid biopsy and correlative clinical implications.

  • Jorge J. Nieva, MD, has clinical interests in biomarker development and predictive analytics of cancer outcomes.  He develops tools across technology platforms ranging from blood, image, and wearable platforms to monitor cancer patients and predict survival and toxicity events.

    As the research lead for the thoracic oncology program, he is responsible for maintain a portfolio of clinical trials in thoracic as well as head/neck oncology.

  • As part of a RO1 grant, Dr. Pinski is extracting DNA and RNA from primary tumors and DNA from buffy coats from prostate cancer patients who participate in a large, phase III SWOG clinical trial (1500 patients) to assess the clinical benefits of two different hormonal therapy approaches. DNA and RNA samples will be sequenced and the molecular signatures then correlated with clinical outcome parameters.

    Dr. Pinski’s lab is developing CAR-T cells targeting cancer cells which express LHR. He is studying the efficacy of this approach in various in vitro and in vivo ovarian and prostate cancer models. He is also working on methods to improve the penetration of CAR-T cells into the tumor microenvironment and on decreasing their treatment toxicity.

  • Zahoor’s research interests include clinical and translational research in renal cell carcinoma. He is particularly interested in clinical trial development, immuno-oncology and biomarker development (especially imaging based) in RCC.