Jewish General Hospital
Oncology Center, E-175
3755 Cote Saint Catherine Road
Montreal, Quebec
H3T 1E2

Tel.: 514-340-8222
Lawrence C. Panasci
 
Senior Investigator, Lady Davis Institute
Associate Director of Oncology Department, Jewish General Hospital
Professor, Department of Medicine and Oncology, McGill University
Director of Medical Oncology, Department of Oncology, McGill University
 
Dr. Panasci's Publications Indexed on PubMed
 
A graduate of Georgetown University Medical School in Washington, DC, Dr. Lawrence Panasci pursued his internship and residency at Case Western Reserve University in Cleveland. He subsequently held a research oncology fellowship at Georgetown and a clinical fellowship with the American Cancer Society, before serving as a visiting fellow at the Instituto Nazionale Tumori in Milan. He joined the faculty of McGill University and the staff of the Jewish General Hospital in Montreal in 1980. 
 
Major Research Activities
 
(1) The development of chronic lymphocytic leukemia (CLL) as an in-vitro/in-vivo model to investigate nitrogen mustard drug resistance. The initial investigations done in Dr. Panasci’s laboratory in the 1980's helped to establish CLL as an excellent clinically relevant model for use in in-vitro/in-vivo correlations. Over the last fifteen years, the lab has refined the model and further elaborated its investigations/results, leading to thirteen excellent publications on CLL vis-à-vis nitrogen mustard drug resistance.

(2) The development of a chloroethylnitrosourea analogue, SarCNU, based on its specific uptake into glioma cells via the extra-neuronal monoamine transporter (EMT/ OCT3). Dr. Panasci’s laboratory found that SarCNU was more active than BCNU, once the standard chemotherapy for gliomas. It has been determined that SarCNU was selectively transported into some glioma cell lines via EMT and demonstrated that this was important for its selective cytotoxicity. Following a presentation of the results before the National Cancer Institutes, extensive toxicology studies led to Phase I trials of SarCNU in cancer patients, based on experimental evidence developed in this laboratory.

(3) Over the past decade, extensive molecular/functional characterization of the DNA repair pathways by other scientists have allowed for a more precise determination of the details of DNA repair vis-à-vis DNA cross-linking drug resistance, including the involvement of the Rad51 homologous recombinational repair pathway, transcriptional-related DNA repair (XPD), and nonhomologous repair (NHEJ including DNA-PK).

(4) The identification of gleevec as a sensitizing agent to chlorambucil in CLL, in collaboration with Dr. Aloyz. The in-vitro results of gleevec sensitization of CLL lymphocytes to chlorambucil by inhibition of c-abl activation, with subsequent inhibition of Rad51 phosphorylation/foci resulting in presumably less repair of chlorambucil-induced cytotoxic DNA lesions, offered a rational approach to combination therapy (gleevec/chlorambucil) in CLL patients. A clinical trial in CLL tested this combination and initial results show good anti-tumor activity in patients.

(5) The identification of DNA-PK inhibitors as important sensitizers of chlorambucil in CLL lymphocytes, also in collaboration with Dr. Aloyz. This exciting new development suggests that inhibition of the DNA-PK pathway also sensitizes CLL lymphocytes to chlorambucil. They are now collaborating with Luitpold Pharmaceuticals to test their specific DNA-PK inhibitors which are more soluble. Clinical trials of these new DNA-PK inhibitors will be done if animal studies demonstrate good activity with acceptable pharmacokinetic properties.
 
Recent Publications
 
Sahebjam S, Aloyz R, Pilavdzic D, Brisson ML , Ferrario C, Bouganim N, Cohen V, Miller WHJr., and Panasci LC. “Ki 67 is a major but not the sole determinant of Oncotype Dx recurrence score.” Brit J Cancer.

Amrein L, Rachid Z, Jean-Claude B, Soulières D, Aloyz R, Panasci L. ZRF4, a combi-molecule with increased efficacy as compared with the individual components in chronic lymphocytic leukemia lymphocytes in vitro. Leukemia. 2011 25(9):1512-6.

Amrein L, Loignon M, Goulet AC, Dunn M, Jean-Claude B, Aloyz R, Panasci L. “Chlorambucil cytotoxicity in malignant B lymphocytes is synergistically increased by 2-(morpholin-4-yl)-benzo[h]chomen-4-one (NU7026)-mediated inhibition of DNA double-strand break repair via inhibition of DNA-dependent protein kinase.” J Pharmacol Exp Ther. 2007 Jun;321(3):848-55.
Snapshot

Dr. Panasci is Associate Director of Oncology at the Jewish General Hospital and Professor of Oncology at McGill University.

His lab at the Lady Davis Institute is actively engaged in several research projects to test novel approaches to the treatment of chronic lymphocytic leukemia.

 
 
Important Links
Dr. Panasci's Profile at the Division of Experimental Medicine, McGill University
 
Support research at the Lady Davis Institute - Jewish General Hospital