Brent Passer

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-6798


bpasser@partners.org

Brent Passer

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Instructor, Surgery, Harvard Medical School
  • Instructor, Neurosurgery, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

The major focus of my research has been on the application of replication-competent oncolytic herpes-simplex viruses (oHSV) for the treatment of prostate cancer. Oncolytic HSV-based vectors can replicate within and kill tumor cells (oncolysis), sparing normal cells. One major drawback is its limited capacity to spread intercellularly and kill neighboring cancer cells. To improve the clinical utility of oHSV-based therapies for prostate cancer, my ongoing studies have focused on the identification of chemotherapeutic agents and/or small molecule compounds that modulate important prostate cancer cell pathways and, when paired with appropriate oHSV vectors can increase oncolytic cancer cell destruction. I have pursued this line of research using two interrelated strategies: 1) Screened several FDA-approved chemotherapeutic agents in conjunction with oHSV to identify a synergistic combination that results augmented cell death both in vitro and in vivo. 2) Undertook an unbiased high-throughput chemical library screen to identify small molecule compounds that promote augmented oHSV spread in human prostate cancer cells. The coupling of oHSV virotherapy with small molecule discovery has allowed us to uncover novel pathways of viral oncolysis in prostate cancer and moreover, has led to increased efficacy in preclinical testing.

Publications

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  • Playa H, Lewis TA, Ting A, Suh BC, Muñoz B, Matuza R, Passer BJ, Schreiber SL, Buolamwini JK. Dilazep analogues for the study of equilibrative nucleoside transporters 1 and 2 (ENT1 and ENT2). Bioorg Med Chem Lett 2014; 24:5801-4. PubMed
  • Castelo-Branco P, Passer BJ, Buhrman JS, Antoszczyk S, Marinelli M, Zaupa C, Rabkin SD, Martuza RL. Oncolytic herpes simplex virus armed with xenogeneic homologue of prostatic acid phosphatase enhances antitumor efficacy in prostate cancer. Gene Ther 2010; 17:805-10. PubMed
  • Passer BJ, Cheema T, Zhou B, Wakimoto H, Zaupa C, Razmjoo M, Sarte J, Wu S, Wu CL, Noah JW, Li Q, Buolamwini JK, Yen Y, Rabkin SD, Martuza RL. Identification of the ENT1 antagonists dipyridamole and dilazep as amplifiers of oncolytic herpes simplex virus-1 replication. Cancer Res 2010; 70:3890-5. PubMed
  • Passer BJ, Castelo-Branco P, Buhrman JS, Varghese S, Rabkin SD, Martuza RL. Oncolytic herpes simplex virus vectors and taxanes synergize to promote killing of prostate cancer cells. Cancer Gene Ther 2009; 16:551-60. PubMed
  • Fulci G, Passer B. Analysis of HSV oncolytic virotherapy in organotypic cultures. Methods Mol Biol 2009; 542:75-86. PubMed
  • Castelo-Branco P, Passer BJ, Buhrman JS, Antoszczyk S, Marinelli M, Zaupa C, Rabkin SD, Martuza . An oncolytic herpes simplex virus armed with a xenogeneic homologue of prostatic acid phosphatase enhances anti-tumor efficacy in prostate cancer Gene Ther 2010.