Strategies Against HPV Related Genital Diseases in Women

Summary

Principal Investigator: B J Monk
Abstract: The human papillomavirus (HPV) is a significant etiologic agent in lower female genital tract neoplasia. Novel interactions with other co-carcinogens and/or immuno-deficiency lead to tumorigenesis and cancer progression. However, both the lack of adequate animal models and prospective clinical trials are impediments to the development of effective anti-HPV therapies and prevent a thorough understanding of human interactions with this virus. The objective of this proposal is to support the career development of Bradley J. Monk, M.D. Under the direction of Dr. Luis P. Villarreal, Ph.D., Dr. Monk will evaluate co-carcinogens and anti-viral agents in a recently described severe combined immunodeficiency mouse model using implanted human HPV infected epithelium, cervical intraepithelial neoplasia (CIN). Dr. Monk proposes to study the neoplastic transformation as well as the progression or regression of these cervical tissue implants. The influence of specific promoters or genotoxic compounds (e.g. hormones, nicotine) as well as novel anti-HPV agents (e.g. stimulated immune cells, anti-sense oncogenes) and nutritional supplements (e.g. indole 3-carbinol or I3C) will be studied. In addition, under the direction of Philip J. DiSaia, M.D., a Gynecologic Oncologist; Frank L. Meyskens, M.D., a Medical Oncologist with expertise in Chemoprevention; and Jeffrey S. Weber, M.D., Ph.D., a Medical Oncologist with expertise in Immunology, Dr. Monk will conduct two prospective clinical trials of novel HPV therapies. First, I3C, a compound found in cruciferous vegetables and effective in HPV related laryngeal papillomatosis, will be evaluated in patients with HPV induced genital warts in a randomized phase II trial. Second, a phase I and II study of a DNA plasmid vaccine encoding an immunogenic portion of the HPV type 16 E7 protein is planned among women with CIN. Dr. Monk will focus his career on translational research in the area of anti-HPVmodalities specifically related to female lower genital tract neoplasia. Mentors in Virology, Chemoprevention, Immunology and Gynecologic Oncology will allow Dr. Monk to investigate unique anti-viral agents both in the laboratory and in clinical settings with an emphasis on HPV immunity. This path will develop Dr. Monk into an independent investigator able to study anti-HPV therapies first in animals then in human chemoprevention trials. It is expected that Dr. Monk will have obtained extramural funding for both his laboratory and clinical studies by the end of the period of support requested.
Funding Period: 2001-08-29 - 2006-06-30
more information: NIH RePORT

Top Publications

  1. pmc High-throughput profiling of the humoral immune responses against thirteen human papillomavirus types by proteome microarrays
    Martha Luevano
    Departamento de Bioquimica, Facultad de Medicina, Universidad Autonoma de Nuevo Leon, Monterrey, Mexico
    Virology 405:31-40. 2010
  2. pmc Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study
    Bradley J Monk
    University of California, Irvine Medical Center, Orange, CA 92868, USA
    J Clin Oncol 27:4649-55. 2009
  3. pmc Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study
    Bradley J Monk
    University of California, Irvine Medical Center, Bldg 56, Room 262, 101 The City Dr, Orange, CA 92868 USA
    J Clin Oncol 27:1069-74. 2009
  4. ncbi Phase I/II trial of tremelimumab in patients with metastatic melanoma
    Luis H Camacho
    Oncology Consultants, Department of Research, 920 Frostwood, Ste 780, Houston, TX 77024, USA
    J Clin Oncol 27:1075-81. 2009
  5. pmc Markers of angiogenesis in high-risk, early-stage cervical cancer: A Gynecologic Oncology Group study
    Leslie M Randall
    Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, CA 92868, USA
    Gynecol Oncol 112:583-9. 2009
  6. pmc Which clinical/pathologic factors matter in the era of chemoradiation as treatment for locally advanced cervical carcinoma? Analysis of two Gynecologic Oncology Group (GOG) trials
    Bradley J Monk
    Department of Ob Gyn, Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, CA 92868, and Department of Radiation Oncology, Delaware County Memorial Hospital, Drexel Hill, PA 19026, USA
    Gynecol Oncol 105:427-33. 2007
  7. ncbi Clinical results and quality of life analysis for the MVAC combination (methotrexate, vinblastine, doxorubicin, and cisplatin) in carcinoma of the uterine cervix: A Gynecologic Oncology Group study
    Harry J Long
    Mayo Clinic, Department of Medical Oncology, East 12B Mayo Building, 200 First Street, Southwest, Rochester, MN 55905 0001, USA
    Gynecol Oncol 100:537-43. 2006
  8. ncbi Gene expression profiling of in vitro radiation resistance in cervical carcinoma: a feasibility study
    Devansu Tewari
    Division of Gynecologic Oncology, University of California Irvine Medical Center, 101 The City Drive South, Orange, CA 92868, USA
    Gynecol Oncol 99:84-91. 2005
  9. ncbi Quality of life outcomes from a randomized phase III trial of cisplatin with or without topotecan in advanced carcinoma of the cervix: a Gynecologic Oncology Group Study
    Bradley J Monk
    Division of Gynecologic Oncology, Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, CA, USA
    J Clin Oncol 23:4617-25. 2005
  10. ncbi Rethinking the use of radiation and chemotherapy after radical hysterectomy: a clinical-pathologic analysis of a Gynecologic Oncology Group/Southwest Oncology Group/Radiation Therapy Oncology Group trial
    Bradley J Monk
    Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Chao Family Comprehensive Cancer Center, University of California, Irvine Medical Center, 101 The City Drive, Building 23, Room 107, Orange, CA 92868, USA
    Gynecol Oncol 96:721-8. 2005

Scientific Experts

  • B J Monk
  • Luis H Camacho
  • Harry J Long
  • Martha Luevano
  • Leslie M Randall
  • John P Fruehauf
  • Robert A Burger
  • Devansu Tewari
  • Mina Kalantari
  • D Huw Davies
  • Alejandro Garcia-Carranca
  • Hans Ulrich Bernard
  • Phil L Felgner
  • Hugo A Barrera-Saldana
  • Xiaolin Tan
  • Luisa L Villa
  • Victor Trevino
  • Chunqiao Tian
  • Shu Yuan Liao
  • William A Peters
  • Kathleen M Darcy
  • Richard J Stock
  • J Denis Heck
  • Muthana S Al-Ghazi
  • Ricardo Parker

Detail Information

Publications10

  1. pmc High-throughput profiling of the humoral immune responses against thirteen human papillomavirus types by proteome microarrays
    Martha Luevano
    Departamento de Bioquimica, Facultad de Medicina, Universidad Autonoma de Nuevo Leon, Monterrey, Mexico
    Virology 405:31-40. 2010
    ..Our study introduces a new approach to future evaluation of the overall antigenicity of HPV proteins and cross-reaction between homologous proteins...
  2. pmc Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study
    Bradley J Monk
    University of California, Irvine Medical Center, Orange, CA 92868, USA
    J Clin Oncol 27:4649-55. 2009
    ..Assess toxicity and efficacy of cisplatin (Cis) doublet combinations in advanced and recurrent cervical carcinoma...
  3. pmc Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study
    Bradley J Monk
    University of California, Irvine Medical Center, Bldg 56, Room 262, 101 The City Dr, Orange, CA 92868 USA
    J Clin Oncol 27:1069-74. 2009
    ..The Gynecologic Oncology Group (GOG) conducted a phase II trial to assess the efficacy and tolerability of bevacizumab, a recombinant humanized anti-vascular endothelial growth factor monoclonal antibody...
  4. ncbi Phase I/II trial of tremelimumab in patients with metastatic melanoma
    Luis H Camacho
    Oncology Consultants, Department of Research, 920 Frostwood, Ste 780, Houston, TX 77024, USA
    J Clin Oncol 27:1075-81. 2009
    ..This phase I/II trial was conducted to examine safety of multiple doses of tremelimumab, to further assess efficacy, and to identify an appropriate dosing regimen for further development...
  5. pmc Markers of angiogenesis in high-risk, early-stage cervical cancer: A Gynecologic Oncology Group study
    Leslie M Randall
    Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, CA 92868, USA
    Gynecol Oncol 112:583-9. 2009
    ..To determine whether markers of tumor angiogenesis were associated with progression-free survival (PFS) and overall survival (OS) in women with high-risk, early-stage cervical cancer treated on a phase III trial...
  6. pmc Which clinical/pathologic factors matter in the era of chemoradiation as treatment for locally advanced cervical carcinoma? Analysis of two Gynecologic Oncology Group (GOG) trials
    Bradley J Monk
    Department of Ob Gyn, Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, CA 92868, and Department of Radiation Oncology, Delaware County Memorial Hospital, Drexel Hill, PA 19026, USA
    Gynecol Oncol 105:427-33. 2007
    ..To explore clinical/pathologic factors associated with prognosis of patients with locally advanced cervical carcinoma treated with weekly cisplatin and pelvic radiation...
  7. ncbi Clinical results and quality of life analysis for the MVAC combination (methotrexate, vinblastine, doxorubicin, and cisplatin) in carcinoma of the uterine cervix: A Gynecologic Oncology Group study
    Harry J Long
    Mayo Clinic, Department of Medical Oncology, East 12B Mayo Building, 200 First Street, Southwest, Rochester, MN 55905 0001, USA
    Gynecol Oncol 100:537-43. 2006
    ..The primary endpoint was overall survival (OS), with response rate, progression-free survival (PFS), and quality of life (QOL) as secondary objectives...
  8. ncbi Gene expression profiling of in vitro radiation resistance in cervical carcinoma: a feasibility study
    Devansu Tewari
    Division of Gynecologic Oncology, University of California Irvine Medical Center, 101 The City Drive South, Orange, CA 92868, USA
    Gynecol Oncol 99:84-91. 2005
    ..To determine the feasibility of integrating an in vitro chemo-radiation response assay (IVRRA) with a gene microarray system to investigate the molecular patterns of expression that contribute to radiation resistance in cervical cancer...
  9. ncbi Quality of life outcomes from a randomized phase III trial of cisplatin with or without topotecan in advanced carcinoma of the cervix: a Gynecologic Oncology Group Study
    Bradley J Monk
    Division of Gynecologic Oncology, Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, CA, USA
    J Clin Oncol 23:4617-25. 2005
    ....
  10. ncbi Rethinking the use of radiation and chemotherapy after radical hysterectomy: a clinical-pathologic analysis of a Gynecologic Oncology Group/Southwest Oncology Group/Radiation Therapy Oncology Group trial
    Bradley J Monk
    Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Chao Family Comprehensive Cancer Center, University of California, Irvine Medical Center, 101 The City Drive, Building 23, Room 107, Orange, CA 92868, USA
    Gynecol Oncol 96:721-8. 2005
    ....