Gilda Gali Hillman
Gilda Gali Hillman, PhD
Department of Radiation Oncology, Karmanos Cancer Institute, Wayne State University
4100 John R
Detroit, MI 48201
- Immuno-mediated gene therapy combined with radiotherapy to induce a systemic effect on the primary tumor and metastatic sites.
- Natural compounds as anti-cancer agents to enhance radiotherapy and protect against radiation injury to normal tissues.
- Anti-angiogenic drugs to augment radiation effect on primary tumor and metastatic sites by destroying tumor vasculature.
High dose radiation is effectively used as a conventional therapeutic approach for numerous types of cancers. Considerable tumor debulking can be achieved by radiotherapy for solid cancers, including prostate, kidney, brain and lung cancers. However, radiotherapy can target only a specific tumor site and cannot control the cancer progression in metastatic sites. Additional limitations of radiotherapy are recurrence of tumor growth and radiation-induced injury to normal tissues surrounding the irradiated tumor nodule. Following radiotherapy, tumors often recur locally and cause cancer progression as a result of de novo, as well as acquired radioresistance of tumor cells. Radioresistance is also partly due to focal areas of hypoxic cells resistant to radiation. Early and late effects of radiation cause injury to normal tissues which are surrounding the tumor and are exposed to radiation beams, thereby affecting the quality of life of the patients. We have built orthotopic tumor models in mice by surgically implanting human or mouse tumor cells in different organs to mimic the progression of several malignancies, including prostate, kidney and lung cancers. These models consist of the formation of primary tumors in the organ of origin with spontaneous metastasis to lymph nodes and other organs, and are therefore consistent with the progression of cancer in patients. These pre-clinical models allow us to study the combination of radiotherapy localized to the primary organ bearing the cancer and systemic therapies to enhance the radiation effect on the primary tumor and inhibit tumor growth in metastatic sites. In our pre-clinical translational program, three approaches have been developed to address radioresistance of cancer and inhibit tumor growth in metastatic sites. (i) Radiotherapy to the tumor is combined with immuno-mediated gene therapy to induce a systemic effect on the primary tumor and metastatic sites. (ii) Chemopreventive natural dietary compounds are used as anti-cancer agents to enhance radiotherapy and protect against radiation injury to normal tissues. In particular, soy isoflavones (phytoestrogens or plant estrogens), which are extracted from soy beans, were found to act as radiosensitizers for tumors and radioprotectors for surrounding normal tissues. (iii) The third approach is to use anti-angiogenic drugs to augment radiation effect on primary tumor and metastatic sites by destroying tumor vasculature and preventing neovascularization of recurrent tumors, thus depriving tumor cells of nutrients.
G.G. Hillman, L.A. Reich, S.E. Rothstein, L.M. Abernathy, M.D. Fountain, K.M. Hankerd, C. K. Yunker , J.T. Rakowski, E. Quemeneur, P. Slos. Radiotherapy and MVA-MUC1-IL-2 Vaccine Act Synergistically For Inducing Specific Immunity to MUC-1 Tumor Antigen. Journal for ImmunoTherapy of Cancer, 2017;5:4. This article was highlighted by the Editor-in-Chief of the Journal for ImmunoTherapy of Cancer which is the journal of the Society for ImmunoTherapy of Cancer ( January 18, 2017).
L.M. Abernathy, M.D. Fountain, M.C. Joiner, G.G. Hillman. Innate Immune Pathways Associated with Lung Radioprotection by Soy Isoflavones. Frontiers in Oncology, In Press 2017.
Wuthrick EJ, Curran WJ Jr, Camphausen K, Lin A, Glass J, Evans J, Andrews DW, Axelrod R, Shi W, Werner-Wasik M, Haacke EM, Hillman GG, Dicker AP. A pilot study of hypofractionated stereotactic radiation therapy and sunitinib in previously irradiated patients with recurrent high-grade glioma. Int J Radiat Oncol Biol Phys. 2014;90:369-75.
Hillman GG, Lonardo F, Hoogstra DJ, Rakowski J, Yunker CK, Joiner MC, Dyson G, Gadgeel S, Singh-Gupta V. Axitinib Improves Radiotherapy in Murine Xenograft Lung Tumors. Transl Oncol. 2014:S1936-523300037-0.
Hillman GG, Singh-Gupta V, Lonardo F, Hoogstra DJ, Abernathy LM, Yunker CK, Rothstein SE, Rakowski J, Sarkar FH, Gadgeel S, Konski AA, Joiner MC. Radioprotection of lung tissue by soy isoflavones. J Thorac Oncol. 2013;8:1356-64.
Hillman GG, Singh-Gupta V, Hoogstra DJ, Abernathy L, Rakowski J, Yunker CK, Rothstein SE, Sarkar FH, Gadgeel S, Konski AA, Lonardo F, Joiner MC. Differential effect of soy isoflavones in enhancing high intensity radiotherapy and protecting lung tissue in a pre-clinical model of lung carcinoma. Radiother Oncol. 2013;109:117-25.
Raffoul JJ, Kucuk O, Sarkar FH, Hillman GG. Dietary agents in cancer chemoprevention and treatment. J Oncol. 2012;2012:749310.
Raffoul JJ, Heydari AR, Hillman GG. DNA Repair and Cancer Therapy: Targeting APE1/Ref-1 Using Dietary Agents. J Oncol. 2012;2012:370481.
Singh-Gupta V, Banerjee S, Yunker CK, Rakowski JT, Joiner MC, Konski AA, Sarkar FH, Hillman GG. B-DIM impairs radiation-induced survival pathways independently of androgen receptor expression and augments radiation efficacy in prostate cancer. Cancer Lett. 2012;318:86-92.
Hillman GG, Singh-Gupta V, Runyan L, Yunker CK, Rakowski JT, Sarkar FH, Miller S, Gadgeel SM, Sethi S, Joiner MC, Konski AA. Soy isoflavones radiosensitize lung cancer while mitigating normal tissue injury. Radiother Oncol. 2011;101:329-36
Banerjee S, Kong D, Wang Z, Bao B, Hillman GG, Sarkar FH. Attenuation of multi-targeted proliferation-linked signaling by 3,3'-diindolylmethane (DIM): from bench to clinic. Mutat Res. 2011;728:47-66.
Education and Training:
PhD in Virology (1983): Hebrew University, Jerusalem, Israel
Postdoctoral Associate (1982-1985): Department of Therapeutic Radiology, University of Minnesota, Minneapolis, Minnesota
Cancer Biology Courses Taught:
CB7210 Fundamentals of Cancer Biology
CB7410 Cancer Immunology and Immunotherapy