Martin Brown

Administrative Appointments

• Director, Division of Radiation and Cancer Biology (1984 - 2004)
• Director, Graduate Program in Cancer Biology (1990 - 2002)

Honors and Awards

• Henry S. Kaplan Distinguished Scientist Award, International Association for Radiation Research (2007)
• Weiss Medal, Association for Radiation Research (2001)
• Gold Medal, Americal Society for Therapeutic Radiology and Oncology (1999)
• Bruce Cain Memorial Award, American Association for Cancer Research (1999)

Professional Education

Graduate & Fellowship Program Affiliations

• Cancer Biology
• Comparative Medicine
• Radiation Oncology

Web Site Links

• Brown Lab Web Site

Industry Relationships

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Current Research Interests

We seek to understand the mechanisms responsible for the resistance of solid tumors to cancer therapies and to develop strategies to overcome these resistances. Projects include:

1) Exploitation of tumor hypoxia: Hypoxic cells, characteristic of solid tumors, are resistant to killing by ionizing radiation and by many anticancer drugs. We have developed a drug (tirapazamine or TPZ) activated by low oxygen levels to a toxic species that is selective for solid tumors and is undergoing clinical testing. In addition we have an active program to understand the mechanism and clinical utility of a new hypoxia activated bifunctional mustard, PR-104, a drug that produces DNA interstrand crosslinks and which has entered clinical trials.

2) Identification by HTS of small molecule inhibitors of DNA repair by homologous recombination (HR). This DNA repair pathway is crucial to the repair of the cytotoxic lesions caused by many anticancer agents, such as bifunctional alkylating agents and topoisomerase poisons. Many clinical situations exist whereby inhibiting HR will give a therapeutic gain.

3) Development of anaerobic bacteria as tumor specific gene therapy agents: Certain nonpathogenic Clostridial species proliferate exclusively in the hypoxic/necrotic regions of solid tumors. We have developed shuttle vectors that express an enzyme capable of activating a non-toxic prodrug into a toxic drug in these bacteria and have shown that this enzyme is expressed exclusively in solid tumors. We are currently developing this system as a tumor specific gene therapy system.

4) We are investigating the role of bone marrow derived cells in restoring the tumor vasculature after radiotherapy (which destroys local angiogenesis). This process is known as vasculogenesis. In particular we seek to improve tumor cure rates by radiotherapy by inhibiting the repair of the tumor vasculature in GBM and head and neck tumors by bone marrow derived cells following radiation...

Publications

• Optimized clostridium-directed enzyme prodrug therapy improves the antitumor activity of the novel DNA cross-linking agent PR-104. Liu SC, Ahn GO, Kioi M, Dorie MJ, Patterson AV, Brown JM. Cancer Res. 2008; 68 (19): 7995-8003
• Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: role of bone marrow-derived myelomonocytic cells. Ahn GO, Brown JM. Cancer Cell. 2008; 13 (3): 193-205
• Homologous recombination is the principal pathway for the repair of DNA damage induced by tirapazamine in mammalian cells. Evans JW, Chernikova SB, Kachnic LA, Banath JP, Sordet O, Delahoussaye YM, Treszezamsky A, Chon BH, Feng Z, Gu Y, Wilson WR, Pommier Y, Olive PL, Powell SN, Brown JM. Cancer Res. 2008; 68 (1): 257-65
• Global analysis of gene function in yeast by quantitative phenotypic profiling. Brown JA, Sherlock G, Myers CL, Burrows NM, Deng C, Wu HI, McCann KE, Troyanskaya OG, Brown JM. Mol Syst Biol. 2006: 2 2006.0001
• The role of apoptosis in cancer development and treatment response. Brown JM, Attardi LD. Nat Rev Cancer. 2005; 5 (3): 231-7