Areas of Research: Improving treatment for children, adolescents and young adults with acute lymphoblastic leukemia or Hodgkin’s lymphoma. Reducing the toxic side effects of cancer therapy, particularly those that can affect cognitive function.
My clinical research focuses on improving treatment for children, adolescents and young adults with acute lymphoblastic leukemia or Hodgkin’s lymphoma.
My laboratory background is in the molecular pharmacology of antifolates, such as methotrexate, drugs that exert their antineoplastic effects by interfering with cellular processes dependent on the vitamin folic acid. My current laboratory research centers on reducing the toxicity of anticancer therapy, including that caused by antifolates. Although cure rates for patients with cancer continue to increase, many cancer patients report symptoms suggestive of impaired cognitive function while receiving therapy, including fatigue, short-term memory loss, and diminished concentration. For children, whose brains are continuing to undergo important phases of structural development, the neurotoxic effects of anticancer therapy can be lifelong. The focus of our translational research is studying how cognitive impariment is caused by the complex intersection of host factors (genetic variation), environmental factors (e.g. dietary intake of micro nutrients, such as folate), and treatment factors (chemotherapy and radiation therapy). We are establishing animal models that will improve our understanding of the pathophysiology of treatment-induced neurotoxicity, and allow us to test interventions to eliminate it. In addition, we are attempting to delineate measurable factors in the blood or CSF collected from patients during therapy that will be predictive of neurological impairment after completion of therapy. Once validated prospectively, these predictors can then be used to identify the subset of patients who might derive the greatest benefit from interventions aimed at reducing neurotoxicity.
- Vijayanathan V, Ali N, Gulinello M, Cole PD. Persistent cognitive deficits, induced by intrathecal methotrexate, are associated with elevated CSF concentrations of excitotoxic glutamate analogs and can be reversed by an NMDA antagonist. Behavioural Brain Research. 2011;225(2):491-7.
- Vrooman LM, Neuberg DS, Stevenson KE, Asselin BL, Athale UH, Clavell L, Cole PD, Kelly KM, Larsen EC, Laverdiere C, Michon B, Schorin M, Schwartz CL, Cohen HJ, Lipshultz SE, Silverman LB, and Sallan SE. The low incidence of secondary acute myelogenous leukaemia in children and adolescents treated with dexrazoxane for acute lymphoblastic leukaemia: a report from the Dana-Farber Cancer Institute ALL Consortium. European Journal of Cancer 2011;47: 1373-1379.
- Cole PD, McCarten KM, Drachtman RA, de Alarcon P, Chen L, Trippett TM, Schwartz CL. Early FDG-PET-based Response Evaluation After Treatment with Gemcitabine and Vinorelbine for Refractory Hodgkin Disease: A Children’s Oncology Group Report. Pediatric Hematology and Oncology; 2010; 27(8): 650-7.
- Li Y, Vijayanathan V, Gulinello M, Cole PD. Intrathecal Methotrexate Induces Focal Cognitive Deficits and Decreases Cerebrospinal Fluid Folate in Rats. Pharmacology, Biochemistry and Behavior;2010; 95 (4): 428-33.
- Silverman LB, Supko JG, Stevenson KE, Woodward C, Vrooman LM, Neuberg DS, Asselin BL, Athale UH, Clavell L, Cole PD, Kelly K, Laverdiere C, Michon B, Schorin M, Schwartz CL, O’Brien JE, Cohen HJ, Sallan SE. Intravenous PEG-Asparaginase During Remission Induction in Children and Adolescents with Newly Diagnosed Acute Lymphoblastic Leukemia. Blood 2010; 115(7):1351-3.
- Li Y, Vijayanathan V, Gulinello ME, Cole PD. Systemic Methotrexate Induces Spatial Memory Deficits and Depletes Cerebrospinal Fluid Folate in Rats. Pharmacology, Biochemistry and Behavior 2010: 94(3):454-63.
- Silverman LB, Stevenson K, O’Brien JE, Asselin BL, Athale UH, Clavell L, Cole PD, Kelly K, Laverdiere C, Michon B, Schorin M, Schwartz CL, O’Holleran EW, Neuberg DS, Cohen HJ, Sallan SE. Long-term results of Dana-Farber Cancer Institute ALL Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1981-1995). Leukemia 2010; 24(2): 320-34.
- Cole PD, Beckwith KA, Vijayanathan V, Roychowdhury S, Smith AK, Kamen BA. CSF Folate Homeostasis During Therapy for Acute Lymphoblastic Leukemia. Pediatric Neurology 2009; 40(1): 34-41.
- Cole PD, Schwartz CL, Drachtman RA, de Alarcon PA, Chen L, Trippett T. Phase 2 Study of Weekly Gemcitabine and Vinorelbine for Children with Recurrent or Refractory Hodgkin Disease, A Children's Oncology Group Report. Journal of Clinical Oncology. 2009; 27(9): 1456-61.
- Wollack JB, Makori B, Koneru R, Picinich S, Smith AK, Goldman ID, Qiu A, Cole PD, Glod J, Kamen BA. Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model. Journal of Neurochemistry, 2008; 104(6): 1494-503.
- Cho RC, Cole PD, Sohn KJ, Gaisano G, Croxford R, Kamen BA, Kim YI. Effects of folate and folylpolyglutamyl synthase modulation on chemosensitivity of breast cancer cells. Molecular Cancer Therapeutics, 2007; 6(11): 2909-20.
- Vijayanathan V. Smith AK, Zebala JA, Kamen BA, Cole PD. HPLC Separation of Aminopterin Polyglutamates Within Red Blood Cells of Children Treated for Acute Lymphoblastic Leukemia. Translational Research, 2007; 150(6) 367-73.
- Cole PD, Drachtman RA, Masterson M, Smith AK, Glod J, Zebala JA, Lisi S, Drapala D-A, Kamen BA. Phase IIB Trial Of Aminopterin In Multiagent Therapy For Children With Newly Diagnosed Acute Lymphoblastic Leukemia at High Risk of Relapse. Cancer Chemotherapy and Pharmacology, 2008; 62:65-75.
- Cole PD, Kamen BA. Delayed Neurotoxicity Associated with Therapy for Patients with Childhood Leukemia. Mental Retardation and Developmental Disabilities Research Reviews. 2006; 12(3): 174-83.
- Cole PD, Drachtman RA, Smith AK, Cate S, Larson RA, Hawkins DS, Holcenberg J, Kelly K, Kamen BA. Phase II Trial of Oral Aminopterin for Adults and Children with Refractory Acute Leukemia. Clinical Cancer Research 2005; 11(22): 8089-96.
- Cole PD, Alcaraz MJ, Smith AK, Tan J, Kamen BA. Pharmacodynamic properties of methotrexate and Aminotrexate during weekly therapy. Cancer Chemotherapy and Pharmacology. 2006; 57(6):826-34. Epub 2005 Sep 17.
- Hochhauser CJ, Lewis M, Kamen BA, Cole PD. Steroid Induced Alterations of Mood and Behavior in Children During Treatment for Acute Lymphoblastic Leukemia. Supportive Care in Cancer. 2005; 13(12): 967-74.
- Li WW, Su D, Mizobuchi H, Martin DS, Gu B, Gorlick R, Cole P, and Bertino JR. Status of methylthioadenosine phosphorylase and its impact on cellular response to l-alanosine and methylmercaptopurine riboside in human soft tissue sarcoma cells. Oncology Research, 2004; 14: 373-379.
- Kaufman Y, Drori S, Cole PD, Kamen BA, Sirota J, Ifergan I, Ben Arush MW, Elhasid R, Sahar D, Kaspers GJL, Jansen G, Matherly LH, Rechavi G, Toren A, Assaraf YG. Reduced folate carrier mutations are not the mechanism underlying methotrexate resistance in childhood acute lymphoblastic leukemia. Cancer. 2004; 100(4): 773-82.
- Cole PD, Smith AK, Kamen BA. Osteosarcoma cells, resistant to methotrexate due to nucleoside and nucleobase salvage, are sensitive to nucleoside analogs. Cancer Chemotherapy and Pharmacology 2002; 50(2): 111-6.
- Drachtman RA, Cole PD, Golden CB, James SJ, Melnyk S, Aisner J, Kamen BA. Dextromethorphan is effective in the treatment of subacute methotrexate neurotoxicity. Pediatric Hematology and Oncology, 2002; 19(5): 319-327.
- Cole PD, Gorlick R, Banerjee D, Magill L, Smith A, Kamen BA, Bertino JR. Effects Of Overexpression Of g-Glutamyl Hydrolase (GGH) On Methotrexate Metabolism And Resistance. Cancer Research, 2001; 61(11): 4599-4604.
- Cole PD, Suh JS, Onel K, Stiles J, Armstrong D, Dunkel IJ. Benign Outcome Of RSV Infection In Children with Cancer. Medical and Pediatric Oncology, 2001; 37(1): 24-9.
- Cole PD, Stiles J, Boulad F, Small TN, O’Reilly RJ, George D, Szabolcs P, Kiehn TE, Kernan NA. Successful treatment of Human Herpes Virus-6 encephalitis in a bone marrow transplantation recipient. Clinical Infectious Diseases, 1998; 27:653-4.
- Cole P, Ladanyi M, Gerald WL, Cheung N-K V, Kramer K, LaQuaglia MP, Kushner BH. Synovial sarcoma mimicking desmoplastic small round-cell tumor: critical role for molecular diagnosis. Medical and Pediatric Oncology, 1999; 32: 97-101.
- Gorlick R, Cole P, Banerjee D, Longo G, Li WW, Hochhauser D, Bertino JR. Mechanisms of methotrexate resistance in acute leukemia: Decreased transport and polyglutamylation. Advances in Experimental Medicine & Biology, 1999:457:543-50.
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