Dr. Forsyth

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Dr. Peter Forsyth

Director Southern Alberta Cancer Research Institute

Associate Director Research Tom Baker Cancer Centre

Professor of Oncology
University of Calgary

HRIC 2AA19, 3330 Hospital Dr. NW

Calgary, AB T2N 4N1

Current Appointments:

Director	Southern Alberta Cancer Research Institute
Associate Director , Research	Tom Baker Cancer Centre
Professor	Department of Oncology and Clinical Neurosciences Faculty of Medicine, University of Calgary Tom Baker Cancer Centre

Education and Training:

1993	Post-doctoral fellowship	Neuro-oncology Memorial Sloan-Kettering Cancer Center New York, New York
1991	Residency	Neurology Mayo Clinic Rochester, Minnesota
1988	Internship	Medicine University of Toronto Toronto, Ontario
1987	Doctor of Medicine	Medicine McMaster University Hamilton, Ontario
1984	M.A.	Physiological Psychology McMaster University Hamilton, Ontario
1983	B.Sc.	Psychology McMaster University Hamilton, Ontario

Overview of Research Program:

Dr Forsyth’s research focuses on the molecular genetics of malignant gliomas, metastasis, and the treatment of malignant gliomas with viral therapies. He I sdedicated to improving the treatment and care of patients with malignant brain tumors through "translational" research. As a clinician Dr Forsyth is developing a new approach to treatment that could offer new hope to patients.

New treatments are urgently needed for a type of brain cancer called Malignant Glioma. Even with the best treatments that are currently available (largely chemotherapy, surgery and radiation) patients with this uncommon but aggressive cancer survive on average just one year! " The work that I do is driven by trying to discover better treatments for this kind of cancer". We work in two areas:

The use of viruses to kill brain cancers.

We’ve discovered that a number of viruses share a useful property: they can infect and kill cancer cells but leave normal cells relatively unaffected. When we first discovered this in 1998 we found it shocking that a particular virus (in this case called reovirus) would cause only mild flu like symptoms in patients, but was very powerful at destroying cancer cells. We have gone on to test this idea in patients with a number of different kinds of cancers and are trying to better understand how these viruses might be used to cure cancers. In the meantime, in a National and International collaboration, we’re now examining a number of other viruses to determine how they work and the best way to use them to treat cancer.

Focus on blocking invasion.

We’re finding ways to block the machinery that cancer cells use to invade into normal tissue. In the case of the brain this is a particularly challenging problem because brain cancer cells invade the normal brain, where they become difficult to reach with "local" treatments such as surgery or radiation. We’ve uncovered a molecular switch that’s coincidently used by nerve cells in the brain to stop growth. But in a nefarious maneuver brain cancer cells actually use the same switch that nerve cells use as a brake but use it as an accelerator to spread throughout the brain. We have been working to understand exactly how this occurs and have developed treatments to block this effect. It turns out that some of these treatments are already used for patients with other neurological diseases which will make it easier to test these treatments in patients.

We believe that these are very promising and exciting areas of cancer treatment that will potentially become successful treatments for patients with many different types of cancer. Since brain tumors are one of the deadliest forms of cancer and in one of the most sensitive areas of the body, we believe that "if it works there it can work anywhere".

Currently Held Research Support:

Agency	Project Title	Investigators	Total Funding	Term
Kids Cancer Care Foundation	Development of Vesicular Stomatitis Virus (VSV) and Myxoma Virus as Experimental Treatments for Medulloblastoma (MB)	Forsyth, P.	$200,000	2007-2010
National Cancer Institute of Canada	Canadian Oncolytic Virus Consortium	PI: J. Bell; Co-Appl. P. Forsyth & 4 others	$7,200,000	2007-2012
Alberta Cancer Board Legacy Grant	Establishing a platform for the development of molecular and experimental therapeutics us malignant gliomas as a target disease	Co PIs: Steve Robbins & P. Forsyth.	$480,600	2007-2009
Alberta Cancer Board Legacy Grant	Developing a platform for metabalomics in cancer: metabalomic analysis of biofluids in brain tumor patients	Co-PIs: Hans Vogel & Jay Easaw Co-appl. P. Forsyth & 6 others	$450,000	2007-2009
Canadian Institutes of Health Research	The neurotrophin receptor p75 mediates invasion in gliomas	Forsyth, P.	$691,548	2005-2010
NCIC	Reovirus as an oncolytic agent in human malignant gliomas (MG)	Forsyth, P.	$995,500	2006-2011

Recent Publications: (2003-present)

Cheng T, Forsyth P, Chaudhry A, Morris D, Gluck S, Russell JA, Stewart DA. High-dose thiotepa, busulfan, cyclophosphamide and ASCT without whole-brain radiotherapy for poor prognosis primary CNS lymphoma. Bone Marrow Transplant. 31: 679-85, 2003.

Forsyth P, Weaver S, Fulton D, Brasher PMA, Sutherland G, Stewart D, Hagen NA, Barnes P, Cairncross JG, DeAngelis LM. Difficulties in Answering an Important Question in Neuro-Oncology: Prophylactic anticonvulsants in Patients with Brain Tumors. The Canadian Journal of Neurological Sciences. 30: 106-112, 2003. (see editorial in same issue by Mason W.P., pg 89-90).

Nuttall Robert K., Pennington, Caroline J., Taplin, Jennifer, Wheal, Alison, Yong, V. Wee, Forsyth, Peter, Edwards, Dylan R. Elevated membrane-Type Matrix Metalloproteinases in Gliomas Revealed by Profiling Proteases and Inhibitors in Human Cancer Cells. Molecular Cancer Research 1: 333-45, 2003.

Yang, W.,* Senger, D.,* Muzik, H., Shi, Z.Q., Johnson, D., Brasher, P.M.A., Rewcastle, N.B., Hamilton, M., Rutka, J., Wolff, J., Wetmore, C., Curran, T., Lee, P.W.K., Forsyth. P.A. Reovirus prolongs survival and reduces the frequency of spinal and leptomeningeal metastases from medulloblastoma. Cancer Research 63, 3162-3172, 2003

Senger D, Cairncross JG, Forsyth PA. Long-term survivors of glioblastoma: statistical aberration or important unrecognized molecular subtype? Cancer J. 9(3):214-21, 2003.

Lauren E A, Moskowitz CH, Mason WP, Crump M, Stewart D, Forsyth P, Paleologos N, Correa DD, Anderson ND, Caron D, Zelenetz A, Nimer SD, DeAngelis LM. Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis. J Clin Oncol. 15;21(22):4151-6, 2003.

Belanger K, MacDonald D, Cairncross G, Gertler S, Forsyth P, Burdette-Radoux S, Bergeron J, Soulieres D, Ludwin S, Wainman N, Eisenhauer E. A phase II study of topotecan in patients with anaplastic oligodendroglioma or anaplastic mixed oligoastrocytoma. Invest New Drugs.21(4):473-80, 2003.

Abrey LE, Childs BH, Paleologos N, Kaminer L, Rosenfeld S, Salzman D, Finlay JL, Gardner S, Peterson K, Hu W, Swinnen L, Bayer R, Forsyth P, Stewart D, Smith AM, Macdonald DR, Weaver S, Ramsey DA, Nimer SD, DeAngelis LM, Cairncross JG. High-dose chemotherapy with stem cell rescue as initial therapy for anaplastic oligodendroglioma. J Neurooncol. 65(2):127-34, 2003

Abrey LE, Moskowitz CH, Mason WP, Crump M, Stewart D, Forsyth P, Paleologos N, Correa DD, Anderson ND, Caron D, Zelenetz A, Nimer SD, DeAngelis LM. Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis. J Clin Oncol. 21(22):4151-6, 2003.

Vieyra D, Senger DL, Toyama T, Muzik H, Brasher PM, Johnston RN, Riabowol K, Forsyth PA. Altered subcellular localization and low frequency of mutations of ING1 in human brain tumors. Clin Cancer Res. 9(16):5952-61, 2003.

Fallon KB, Palmer CA, Roth KA, Nabors LB, Wang W, Carpenter M, Banerjee R, Forsyth P, Rich K, Perry A : Prognostic value of 1p, 19q, 9p, 10q, and EGFR- FISH analyses in recurrent oligodendrogliomas. J Neuropathol Exp Neurol. 63(4):314-322, 2004

Megyesi JF, Kachur E, Lee DH, Zlatescu MC, Bethensky RA, Forsyth PA, Okada Y, Sasaki H, Mizoguchi M, Louis DN, Cairncross DG. Imaging correlates of molecular signatures in oligodendropgliomas. Clinical Cancer Research, 10:4303-4306, July 1, 2004.

Yang WQ, Senger DL, Lun XQ, Muzik H, Shi ZQ, Dyck RH, Norman K, Brasher PM, Rewcastle NB, George D, Stewart D, Lee PW, Forsyth PA. Reovirus as an experimental therapeutic for brain and leptomeningeal metastases from breast cancer. Gene Ther.;11(21):1579-89, November 2004.

Roa W, Brasher PM, Bauman G, Anthes M, Bruera E, Chan A, Fisher B, Fulton D, Gulavita S, Hao C, Husain S, Murtha A, Petruk K, Stewart D, Tai P, Urtasun R, Cairncross JG, Forsyth P. Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol. 2004 May 1;22(9):1583-8. Epub March 29 2004.

Yang WQ, Lun X, Palmer C, Wilcox ME, Muzik H, Shi ZQ, Dyck R, Coffey M, Thompson, B, Hamilton M, Nishikawa SG, Brasher P, Fonseca K, George D, Rewcastle NB, Johnston R, Stewart D, Lee P, Senger D, Forsyth P. Efficacy and Safety Evaluation of Human Reovirus Type 3 in Immunocompetent Animals: Racine and Nonhuman Primates. Clinical Cancer Research, 15;10(24):8561-76, 2004

Kirby S, Gertler SZ, Mason W, Watling C, Forsyth P, Aniagolu J, Stagg R, Wright M, Powers J, Eisenhauer EA. A Phase II study of T138067-sodium in patients with malignant glioma. A trial of the NCI Canada Clinical Trials Group (NCIC CTG), Neuro-Oncology [serial online], February 17, 2005. URL http://neuro-oncology.mc.duke.edu. & Neuro-oncol. 7(2):183-8, 2005.

Thirukkumaran CM, Luider JM, Stewart DA, Alain T, Russsell JA, Auer IA, Forsyth P & Morris DG. Biological Purging of Breast Cancer Cell Lines using a Replication-Competent Oncolytic Virus in Human Stem Cell Autografts. Bone Marrow Transplant. 35(11) 1055-64, 2005

Lun XQ*, Yang WQ*, Alain T, Shi ZS, Muzik HM, Barrett JW, McFadden G, Bell J, Hamilton MG, Senger DL, PA Forsyth. Myxoma Virus is a Novel Oncolytic Virus with Significant Anti-tumor Activity Against Experimental Human Gliomas. Cancer Research 65: 9982-90, 2005.

Zhou Y, Zhang J, Liu Q, Bell R, Muruve DA, Forsyth P, Arcellana-Panlilio M, Robbins S, Yong VW. The chemokine GRO-{alpha} (CXCL1) confers increased tumorigenicity to glioma cells. Carcinogenesis. 26 (12) 2058-68, 2005.

Taphoorn MJB, Stupp R, Coens C, Osoba D, Kortmann R, van den Bent MJ, Mason W, Mirimanoff RO, Baumert BG, Eisenhauer E, Forsyth P, Bottomley A. Health-related quality of life in a randomised controlled trial in glioblastoma patients: a joint European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumour Group/Radiotherapy Group and National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) study. Lancet Oncology. 6 (12) 937-44, 2005

Abrey LE, Childs BH, Paleologos N, Kaminer L, Rosenfeld S, Salzman D, Finlay JL, Gardner S, Peterson K, Hu W, Swinnen L, Bayer R, Forsyth P, Stewart D, Smith AM, Macdonald DR, Weaver S, Ramsey DA, Nimer SD, DeAngelis LM, Cairncross JG, High Dose Chemotherapy with Stem Cell Rescue as Initial Therapy for Anaplastic Oligodendroglioma: Long term follow up. Neuro-oncol. Apr;8(2):183-8, 2006.

Levin VA, Phuphanich S, Yung WKA, Forsyth PA, Del Maestro R, Perry JR, Fuller GN, Elliot M, Baillet M. Randomized, double-blind, placebo-controlled trial of Marimastat in glioblastoma multiforme patients following surgery and irradiation (bigstar). J. Neurooncol. 78(3) 295-302, 2006.

Tang P, Roldan G, Brasher PMA, Fulton D, Roa W, Murtha A, Cairncross JG, Forsyth PA. A Phase II Study of Carboplatin and Chronic High–Dose Tamoxifen in Patients with Recurrent Malignant Glioma. J. Neurooncol. 78(3): 311-6, 2006

Moss EL, Simpson SA, Pelletier G, Forsyth PA. An Open-label Study of the Effects of Bupropion SR on Fatigue, Depression and Quality of Life of Mixed-Site Cancer Patients and their Partners. Psycho-Oncology 15: 259-267, 2006.

Alain T, Johnston KM, RN, Urbanski S, Kossakowska A, Forsyth PA*, Lee PWK*. Reovirus has in vivo oncolytic effect on cells cured of reovirus in vitro. British Journal of Cancer 95: 1020-7, 2006. (*senior authorship shared).

Lun XQ, Senger DL, Alain T , Parato K, Stojdl D, Lichty B, Johnston RN, Hamilton MG, Parney I, Bell JC, Forsyth PA. Recombinant Vesicular Stomatitis Virus (VSV^{∆M51) prolongs survival and targets multi-focal and invasive gliomas when administered intravenously. JNCI 98: 1546-57, 2006.}

Kim M, Egan C, Alain T, Urbanski S, Lee PWK, Forsyth PA, Johnston RN. Acquired resistance to reoviral oncolysis in Ras-transformed fibrosarcoma cells. Oncogene 26: 4124-34, 2007.

Power AT, Wang J, Falls T, Paterson J, Parato K, Lichty BD, Stojdl DF, Forsyth PA, Atkins H, Bell JC. Carrier Cell-based Delivery of an Oncolytic Virus Circumvents Antiviral Immunity. Mol Ther. 15: 123-30, 2007.

Alain T, Kim T, Liacini H, Senger D, Forsyth PA. Proteolytic disassembly is a critical determinant of reovirus oncolysis. Mol. Ther. 15: 1512-21, 2007.

a. See Commentary Lemay, Tumilasci, Hiscott. Mol. Ther. 15: 1406-14-7, 2007.

Lun XQ, Zhou H, Alain T, Sun B, Wang L, Barrett, Stanford MM, McFadden G, Senger D, Forsyth PA. Targeting human medulloblastoma: oncolytic virotherapy with myxoma virus is enhanced by rapamycin. Cancer Research 67: 8818-8827, 2007.

Johnston ALM, Lun XQ, Hempstead BL, Robbins, SM, Forsyth PA* & Senger DL* The Neurotrophin Receptor p75 Mediates Glioma Invasion. PLoS Biology 5: 1723, 2007. *senior authorship is shared; *PF is corresponding author.

Highlighted in Nature Reviews Neuroscience, Sept 20th 2007.

Highlighted in Nature Clinical Practice Neurology, 3: 597, 2007.

Mauer M, Stupp R, Taphorn M, Coens C, Osoba D, Marosi C, Wong R, de Witte o, Cairncross JG, Efficace1 F, Mirimanoff RO, Forsyth P, van den Bent MJ, Weller M and Bottomley A. The prognostic value of health-related quality-of-life data in predicting survival in glioblastoma cancer patients: results from an international randomised phase III EORTC Brain Tumour and Radiation Oncology Groups, and NCIC Clinical Trials Group study. British Journal of Cancer 97:302-7, 2007.

Barrett JW, Alston LR, Wang F, Stanford MM, Gilbert PA, †, Gao X, Jimenez J, Villeneuve D, Forsyth P, McFadden G. Identification of host range mutants of myxoma virus with altered oncolytic potential in human glioma cells. J of Neurovirology 13: 549-60, 2007.

Mason WP, Maestro RD, Eisenstat D, Forsyth P, Fulton D, Laperriere N, Macdonald D, Perry J, Thiessen B; for the Canadian GBM Recommendations Committee. Canadian recommendations for the treatment of glioblastoma multiforme. Curr Oncol. 2007 Jun;14(3):110-7.

Alain T, Wong JF, Endersby R, Urbanski SJ, Lee PW, Muruve DA, Johnston RN, Forsyth PA, Beck PL. Reovirus decreases azoxymethane-induced aberrant crypt foci and colon cancer in a rodent model. Cancer Gene Ther 14: 867-872, 2007.

Roldan G, .Scott J, George D, Easaw J, Parney I, Cairncross JG, Forsyth PA*, Yan E. Leptomeningeal disease from oligodendroglioma: clinical and molecular analysis. Canadian Journal of Neurological Sciences (in press). 2008. *corresponding author; senior authorship is shared.

Wu Y*, Lun XQ*, Zhou H, Sun B, Bell JC, Barrett J, McFadden G, Biegel JA, Senger DL, Forsyth, PA. Oncolytic efficacy of recombinant vesicular stomatitis virus (VSVΔM51) and myxoma virus in experimental models of malignant rhabdoid tumours. Clinical Cancer Research 14:1218-27, 2008.

Forsyth PA
, Roldan G, George D, Wallace C, Palmer C, Morris DG, Cairncross G, Vallee Matthews M, Markert J, Gillespie GY, Coffey M, Thompson B, Hamilton M. A phase I trial of intratumoral (i.t.) administration of reovirus in patients with histologically confirmed recurrent malignant gliomas (MGs). Mol. Ther. 16: 627-32, 2008.

Brown R, Zlatescu M, Sijben A, Roldan G, Easaw J, Forsyth P, Parney I, Sevick R, Yan E, Demetrick D, Schiff D, Cairncross JG, Mitchell R. Detecting Genetic Signatures in Oligodendroglioma Non-Invasively Using MR. Clinical Cancer Research 14: 2357-2362, 2008.

Roldán G, Brasher P, Vecil , Senger D, Rewcastle B, Cairncross G, Forsyth P*, Hamilton M. Population-based study of medulloblastoma: outcomes in Alberta from 1975 to 1996. Can J Neurol Sci 35:210-5, 2008 *senior authorship is shared; *PF is corresponding author.

Mohile NA, Forsyth PA, Stewart D, Raizer JJ, Paleologos N, Kewalramani T, Louis DN, Cairncross JG, Abrey LE. A phase II Study of Intensified Chemotherapy Alone as Initial Treatment for Newly Diagnosed Anaplastic Oligodendroglioma: An Interim Analysis. Journal of Neuro-oncology (epub May 6th), 2008.

Lun QX, Jang J, Tang N, Deng H, Fortino M, Stief AE, Bell JC, Stojdl DF, Nutt CL, Senger DL, Forsyth PA*, McCart*. Efficacy of systemically administered oncolytic vaccinia virotherapy for malignant gliomas is enhanced by combination therapy with rapamycin or cyclophosphamide. Submitted 2008. *senior authorship is shared

Kelly JJP, Chojnacki A, Lun XQ, Sun B, Senger D, Forsyth PA, Auer RN, Parney IF, Weiss S. Culture and characterization of mitogen-independent human brain tumor stem cells. (submitted to Cancer Research).

Thiessen B, Stewart C, Tsao M, Kamel-Reid S, Schaiquevich P, Mason W, Easaw J, Belanger K, Forsyth PA, McIntosh L, Eisenhauer E. A Phase I/II Trial of Laptinib (GW572016) in Recurrent Glioblastoma Multiforme: Clinical outcomes, pharmacokinetics and molecular correlation. (submitted), 2008.