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Patrick Reynolds, M.D., Ph.D.
M.D. University of Texas Southwestern Medical School, Dallas, TX
Ph.D. Cell Biology - University of Texas at Austin
Professor of Cell Biology & Biochemistry, Internal Medicine, and Pediatrics
Director, Cancer Center
Texas Tech University Health Sciences Center
3601 4th Street
Lubbock, Texas 79430
Phone: (806) 743-1558
School of Medicine Cancer Center
Developmental therapeutics of adult and pediatric cancers in both laboratory and clinical studies. Types of drugs studied include retinoids, "vitamin A derivatives" as tumor-selective differentiation or cytotoxic agents and drugs such as depletors of glutathione or Bcl-2 inhibitors that overcome resistance to traditional cytotoxic agents. Other research identifies molecular mechanisms of drug resistance that may provide novel therapeutic targets in childhood and adult cancers, development of novel preclinical testing models for childhood and adult cancer drug development, and clinical trials testing novel therapeutic approaches for cancer.
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(selected from 180 peer-reviewed publication)
- Reynolds CP, Biedler JL, Spengler BA, Reynolds DA, Ross RA, Frenkel EP, Smith RG. Characterization of human neuroblastoma cell lines established before and after therapy. J National Cancer Institute 76:375 387, 1986.
- Wada RK, Seeger RC, Brodeur GM, Rayner SA, Tomayko MM, Reynolds CP: N-myc expression in human neuroblastoma cell lines without N-myc gene amplification, Cancer 72:3346-3354, 1993.
- Villablanca JG, Avramis V, Khan A, Matthay KK, Ramsay NKC, Seeger RC, Reynolds CP: Phase I trial of 13-cis- retinoic acid (cRA) in neuroblastoma patients following bone marrow transplantation (BMT). J Clinical Oncology 13:894-901, 1995.
- Keshelava N, Seeger RC, Groshen S, Reynolds CP: Drug resistance patterns of human neuroblastoma cell lines derived from patients at different phases of therapy. Cancer Research 58:5396-5405, 1998.
- Matthay KK, Villablanca JG, Seeger RC, Stram DO, Harris RE, Ramsay NK, Swift P, Shamada H, Black CG, Brodeur GM, Gerbing R, Reynolds CP: Treatment of high risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. New England J Medicine 341:1165-1173, 1999.
- Maurer BJ, Cabot MC, Reynolds CP: Synergistic cytotxicity in solid tumor cell lines of N-(4-hydroxypheynl)- retinamide and modulators of ceramide metabolism. J National Cancer Institute 92:1897-1908, 2000.
- Keshelava N, Zuo JJ, Chen P, Waidyaratine SN, Luna MC, Gomer CJ, Triche TJ, Reynolds CP: Loss of p53 function confers high-level multi-drug resistance in neuroblastoma cell lines. Cancer Research 61:6185-6193, 2001.
- Anderson C, Reynolds CP: Syngergistic cytotoxicity of buthionine sulfoximine (BSO) and melphalan/BSO in combination for neuroblastoma cell lines derived after myeloablative therapy. Bone Marrow Transplantation 30:135-140, 2002.
- Villablanca JG, Krailo M, Ames MM, Bagniewski PG, Reid JM, Reynolds CP: A phase I trial of oral (capsular) fenretinide (NSC #374551) in children with high-risk solid tumors (Childrens Cancer Group Study 09709) J Clinical Oncology 24:3423-3430, 2006.
- Keshelava N, Davicioni E, Zesheng Wan Z, Ji L, Sposto R, Triche TJ, Reynolds CP: Inhibition of histone deacetylase (HDAC) 1, a drug target identified by expression profiling, sensitizes multi-drug-resistant neuroblastoma cell lines to cytotoxic agents. J National Cancer Institute 99:1107-19, 2007.
- Frgala T, Kalous O, Proffitt RT, Reynolds CP: A novel cytotoxicity assay with a 4 log dynamic range that identifies synergistic drug combinations. Molecluar Cancer Therapeutics 6:886-89, 2007.
- Maurer BJ, Kalous O, Yesair DW, Wu X, Vratilova J, Maldonado V, Khankaldyyan V, Frgala T, Sun BC, McKee RT, Burgess SW, Shaw WA, Reynolds CP: Improved oral delivery of N-(4-hydroxyphenyl)retinamide with novel LYM-X-SORB™ organized lipid complex in mice. Clinical Cancer Research 13:3079-3086, 2007.
- Kang MH, Wan Z, Kang YH, Locke RS, Reynolds CP: Mechanism of synergy of N-(4-hydroxyphenyl)retinamide and ABT-737 in acute lymphoblastic leukemia cell lines: Mcl-1 inactivation. J National Cancer Institute 100:580-595, 2008.
- Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, Smith M, Anderson B, Villablanca JG, Matthay KK, Shimada H, Grupp SA, Seeger RC, Reynolds CP, Buxton A, Reisfeld RA, Gillies SD, Cohn SL, Maris JM, Sondel PM: Anti-GD2 antibody with GM- CSF, IL2 and isotretinoin for neuroblastoma: A Children’s Oncology Group (COG) phase III study. New England J Medicine 363:1324-1333, 2010. (Faculty of 1000 ranked this paper in top 2% of biology and medicine published papers.)
- Kang MH, Smith MA, Morton CL, Nino Keshelava N, Houghton PJ, Reynolds CP: National Cancer Institute Pediatric Preclinical Testing Program: Model description for in vitro cytotoxicity testing. Pediatr Blood Cancer (EPUB Oct, 2010).
- Hadjidaniel MD and Reynolds CP: Antagonism of cytotoxic chemotherapy in neuroblastoma cell lines by retinoic acid is mediated by the anti-apoptotic Bcl-2 family proteins. Mol Cancer Therapeutics 9:3164-74, 2010.
- Fang H Harned TM, Kalous O, Maldonado V, DeClerck YA, Reynolds CP: Synergistic activity of fenretinide and the Bcl-2 family protein inhibitor ABT-737 against human neuroblastoma. Clinical Cancer Research 17:7093-104, 2011.
- Villablanca JG. London WB, Naranjo A, McGrady MS, Ames MM Joel M. Reid JM, McGovern RM, Buhrow SA, Stranzinger JH, Kitchen BJ, Sondel PM, Parisi M, Shulkin B, Yanik GA, Cohn S, Reynolds CP: Phase II study of oral capsular 4-hydroxyphenylretinamide (4-HPR/fenretinide) in pediatric patients with refractory or recurrent neuroblastoma: A report from the Children’s Oncology Group NSC #374551; IND# 40294. Clinical Cancer Research 17:6858-6866, 2011.
- Xu J, Erdreich-Epstein A, Gonzalez-Gomez I, Melendez EY, Smbatyan G, Moats RA, Rosol M, Biegel J, Reynolds CP: Novel cell lines accurately reflect pediatric brain tumors. J Neurooncology 107:269-80, 2012.
- Sausen M, Leary RJ, Wu J, Reynolds CP, Liu X, Maris J, Blackford A, Parmigiani G, Diaz LA, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE, Hogarty MD: Genomic landscape of the childhood cancer neuroblastoma. Nature Genetics (In Press, 2012)
Curriculum Vitae(Selections from)
History & Education
|1974 ||BA ||Biology - University of Texas at Austin |
|1979 ||MD ||University of Texas Southwestern Medical School, Dallas, TX |
|1979 ||PhD ||Cell Biology - University of Texas at Austin |
Postdoctoral Research Fellowships
|1980 ||University of Texas Southwestern Medical School, Dallas, TX |
|1981 ||Pediatrics, National Naval Medical Center, Bethesda, Maryland |
|1988 ||Gold Medal for Research Achievement awarded by Nihon University, Tokyo, Japan |
|1992 ||Team Physician, 1992 USA Olympic Shooting Team, 25th Olympiad, Barcelona, Spain |
|2004 ||Eurand Prize for Novel Approaches in Oral Drug Delivery by the Controlled Release Society |
|2008 ||Best Clinical Paper Award, Advances in Neuroblastoma Research, Chiba, Japan |
|2011 ||Most cited paper in Clinical Cancer Research, 2009 |
| ||(Clinical Cancer Research 15:1126-1132, 2009) |
National and State Leadership and Advisory Positions
|2000 - Present ||US FDA Pediatric Subcommittee of the Oncologic Drugs Advisory Committee |
|2007 - 2008 ||Natl. Cancer Inst. SBIR/STTR ZRG1 Cancer Drug Dev. + Therapeutics Study Section |
|2008 - Present ||Natl. Inst. Child Health and Development, Best Pharmaceuticals for Children Act Panel |
|2008 - Present ||Chartered member, Natl. Cancer Inst Drug Discovery + Molecular Pharm. Study Section |
|2009 - Present ||Advisory Committee on Childhood Cancer, Cancer Prevention Research Inst of Texas |
|2010 - Present ||Council of Principal Investigators, Texas Cancer Clinical Trials Network |
|2012 - Present ||University Advisory Committee, Cancer Prevention & Research Inst of Texas |
Current Grant Support
Grants as Principal Investigator
|NCI RO1 (CA82830) ||Enhancing the Activity of Alkylating Agents in Neuroblastoma ||1/05-12/13 |
|NCI Contract ||Pediatric Preclinical Testing Program In Vitro Drug Testing Laboratory ||11/04-10/14 |
|NCCF ||Ewings Sarcoma Preclinical Testing Lab ||01/11-12/12 |
|NCI/NCCF ||COG Neuroblastoma Cell Culture Laboratory ||11/08-10/13 |
|Cancer Prevention & Research Institute of Texas (CPRIT): RP10072 ||Enhancing the anti-neuroblastoma activity of fenretinide by identifying and targeting sphingolipid pathways that confer resistance. ||9/10-8/13 |
|CPRIT RP110763 ||Texas Cancer Cell Repository ||06/11-05/14 |
|St. Baldricks ||COG Clinical Trial Access ||01/12-12/13 |
|NCI R21 (CA161889) ||Phase 1 Trial of Fenretinide & Safingol ||08/11-07/13 |
Grants as Co-Investigator
|CPRIT ||Kang, M (PI) ||MCL-1 Promoter Deletion in ALL ||6/10-5/13 |
|Wilson Foundation ||Maurer, BJ (PI) ||Preclinical Studies of Fenretinide in Ovarian Cancer ||11/10-12/12 |
|CPRIT RP10153 ||Gibbs (PI) ||Texac Cancer Research Bank ||09/11-08/13 |