ALAN R EASTMAN

Summary

Affiliation: Dartmouth Medical School
Country: USA

Publications

  1. ncbi Preclinical Development of the Novel Chk1 Inhibitor SCH900776 in Combination with DNA-Damaging Agents and Antimetabolites
    Ryan Montano
    Corresponding Author Alan Eastman, Norris Cotton Cancer Center, Rubin Bldg, Level 6, Dartmouth Medical School, Lebanon, NH 03756
    Mol Cancer Ther 11:427-38. 2012
  2. ncbi Variations in Mre11/Rad50/Nbs1 status and DNA damage-induced S-phase arrest in the cell lines of the NCI60 panel
    Kristen M Garner
    Department of Pharmacology and Toxicology, and Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH 03756, USA
    BMC Cancer 11:206:1-13. 2011
  3. ncbi New targets and challenges in the molecular therapeutics of cancer
    Alan Eastman
    Department of Pharmacology and Toxicology, Dartmouth Medical School, Norris Cotton Cancer Center, Lebanon, NH 03756, USA
    Br J Clin Pharmacol 62:5-14. 2006
  4. ncbi The protein kinase C inhibitor Gö6976 is a potent inhibitor of DNA damage-induced S and G2 cell cycle checkpoints
    Ethan A Kohn
    Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Cancer Res 63:31-5. 2003
  5. ncbi Defective p53 signaling in p53 wild-type tumors attenuates p21waf1 induction and cyclin B repression rendering them sensitive to Chk1 inhibitors that abrogate DNA damage-induced S and G2 arrest
    Aime A Levesque
    Department of Pharmacology and Toxicology and Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH 03756, USA
    Mol Cancer Ther 7:252-62. 2008
  6. ncbi DNA damage-induced S phase arrest in human breast cancer depends on Chk1, but G2 arrest can occur independently of Chk1, Chk2 or MAPKAPK2
    Wen Hui Zhang
    Department of Pharmacology and Toxicology, and the Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA
    Cell Cycle 7:1668-77. 2008
  7. ncbi A novel indolocarbazole, ICP-1, abrogates DNA damage-induced cell cycle arrest and enhances cytotoxicity: similarities and differences to the cell cycle checkpoint abrogator UCN-01
    Alan Eastman
    Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    Mol Cancer Ther 1:1067-78. 2002
  8. ncbi Radiotherapy in conjunction with 7-hydroxystaurosporine: a multimodal approach with tumor pO2 as a potential marker of therapeutic response
    Nadeem Khan
    EPR Center for Viable Systems, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Radiat Res 172:592-7. 2009
  9. ncbi Modulation of cell cycle progression in human tumors: a pharmacokinetic and tumor molecular pharmacodynamic study of cisplatin plus the Chk1 inhibitor UCN-01 (NSC 638850)
    Raymond P Perez
    Section of Hematology Oncology, Department of Medicine, Dartmouth Medical School, Norris Cotton Cancer Center, Lebanon, New Hampshire 03756, USA
    Clin Cancer Res 12:7079-85. 2006
  10. ncbi Abrogation of the S phase DNA damage checkpoint results in S phase progression or premature mitosis depending on the concentration of 7-hydroxystaurosporine and the kinetics of Cdc25C activation
    Ethan A Kohn
    Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 277:26553-64. 2002

Research Grants

  1. CELL DEATH INDUCED BY ANTICANCER AGENTS
    Alan Eastman; Fiscal Year: 2004
  2. CELL DEATH INDUCED BY ANTICANCER AGENTS
    Alan Eastman; Fiscal Year: 2007
  3. Mechanisms of Resistance to Cell Cycle Checkpoint Kinase Inhibitors
    Alan Eastman; Fiscal Year: 2007
  4. 2006 Molecular Therapeutics of Cancer Gordon Research Conference
    Alan Eastman; Fiscal Year: 2007
  5. Cancer Biology and Molecular Therapeutics
    Alan Eastman; Fiscal Year: 2007
  6. Mechanisms of Resistance to Cell Cycle Checkpoint Kinase Inhibitors
    Alan Eastman; Fiscal Year: 2009
  7. Cell Survival Pathways and Inhibitors in Leukemia
    Alan Eastman; Fiscal Year: 2003
  8. CELL DEATH INDUCED BY ANTICANCER AGENTS
    Alan Eastman; Fiscal Year: 1993
  9. ABROGATION OF CELL CYCLE ARREST BY STAUROSPORINE ANALOGS
    Alan Eastman; Fiscal Year: 2001
  10. Mechanisms of Resistance to Cell Cycle Checkpoint Kinase Inhibitors
    ALAN R EASTMAN; Fiscal Year: 2010

Collaborators

  • L D Lewis
  • Raymond P Perez
  • Nadeem Khan
  • Harold Swartz
  • M B Sporn
  • Michael Spinella
  • Gordon Gribble
  • Burton L Eisenberg
  • Eugene Demidenko
  • Aime A Levesque
  • Kristen M Garner
  • Ethan A Kohn
  • Ryan Montano
  • Bethany L Salerni
  • Maroun J Beyrouthy
  • Christina Donnelly
  • Wen Hui Zhang
  • Andrew A Fanous
  • Julie A Vrana
  • Maureen O Ripple
  • Kathryn Chatfield
  • Kyle S MacLea
  • Terrance A Stadheim
  • David Parry
  • Injae Chung
  • Tina C Albershardt
  • Darcy J Bates
  • Christopher H Lowrey
  • Mary P Hever
  • Sarah J Freemantle
  • William B Kinlaw
  • Ethan Dmitrovsky
  • Arne M Olsen
  • Alisa Poh
  • Wen-Hui Zhang
  • Alissa Poh
  • Ruth W Craig
  • Emily S Cleaveland
  • Sahana Kalmadi
  • Edward Bresnick
  • Carolyn J Yoo
  • Nanjoo Suh
  • Neema Ganju
  • Ronald J Krieser
  • Nicola D Ruth
  • Mark Livingstone
  • Mary Kay Brown

Detail Information

Publications21

  1. ncbi Preclinical Development of the Novel Chk1 Inhibitor SCH900776 in Combination with DNA-Damaging Agents and Antimetabolites
    Ryan Montano
    Corresponding Author Alan Eastman, Norris Cotton Cancer Center, Rubin Bldg, Level 6, Dartmouth Medical School, Lebanon, NH 03756
    Mol Cancer Ther 11:427-38. 2012
    ..SCH900776 is currently in phase I clinical trials, and these results provide the rationale and schedule for future clinical trials. Mol Cancer Ther; 11(2); 427-38. ©2011 AACR...
  2. ncbi Variations in Mre11/Rad50/Nbs1 status and DNA damage-induced S-phase arrest in the cell lines of the NCI60 panel
    Kristen M Garner
    Department of Pharmacology and Toxicology, and Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH 03756, USA
    BMC Cancer 11:206:1-13. 2011
    ..The goal of this study was to identify these defects in the NCI60 panel of cell lines and identify compounds that might elicit selective cytotoxicity...
  3. ncbi New targets and challenges in the molecular therapeutics of cancer
    Alan Eastman
    Department of Pharmacology and Toxicology, Dartmouth Medical School, Norris Cotton Cancer Center, Lebanon, NH 03756, USA
    Br J Clin Pharmacol 62:5-14. 2006
    ..These and many other challenges exist in the preclinical and clinical development of these drugs...
  4. ncbi The protein kinase C inhibitor Gö6976 is a potent inhibitor of DNA damage-induced S and G2 cell cycle checkpoints
    Ethan A Kohn
    Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Cancer Res 63:31-5. 2003
    ..These properties make Gö6976 a promising candidate for preclinical and clinical studies...
  5. ncbi Defective p53 signaling in p53 wild-type tumors attenuates p21waf1 induction and cyclin B repression rendering them sensitive to Chk1 inhibitors that abrogate DNA damage-induced S and G2 arrest
    Aime A Levesque
    Department of Pharmacology and Toxicology and Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH 03756, USA
    Mol Cancer Ther 7:252-62. 2008
    ....
  6. ncbi DNA damage-induced S phase arrest in human breast cancer depends on Chk1, but G2 arrest can occur independently of Chk1, Chk2 or MAPKAPK2
    Wen Hui Zhang
    Department of Pharmacology and Toxicology, and the Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA
    Cell Cycle 7:1668-77. 2008
    ..These results show that Chk1, but neither Chk2 nor MK2, is an important regulator of S phase arrest, and suggest that an additional kinase can contribute to the G(2) arrest...
  7. ncbi A novel indolocarbazole, ICP-1, abrogates DNA damage-induced cell cycle arrest and enhances cytotoxicity: similarities and differences to the cell cycle checkpoint abrogator UCN-01
    Alan Eastman
    Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    Mol Cancer Ther 1:1067-78. 2002
    ..Hence, ICP-1 appears to be a more selective inhibitor of the S and G2 cell cycle checkpoint than previously studied analogues and is worthy of study in preclinical tumor models...
  8. ncbi Radiotherapy in conjunction with 7-hydroxystaurosporine: a multimodal approach with tumor pO2 as a potential marker of therapeutic response
    Nadeem Khan
    EPR Center for Viable Systems, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Radiat Res 172:592-7. 2009
    ..This multimodal approach could be used to enhance the outcome of radiotherapy. Furthermore, tumor pO2 could be a potential marker of therapeutic response...
  9. ncbi Modulation of cell cycle progression in human tumors: a pharmacokinetic and tumor molecular pharmacodynamic study of cisplatin plus the Chk1 inhibitor UCN-01 (NSC 638850)
    Raymond P Perez
    Section of Hematology Oncology, Department of Medicine, Dartmouth Medical School, Norris Cotton Cancer Center, Lebanon, New Hampshire 03756, USA
    Clin Cancer Res 12:7079-85. 2006
    ..A phase I trial tested the hypothesis that UCN-01 abrogates cisplatin-induced cell cycle arrest (in tumors) at tolerable doses...
  10. ncbi Abrogation of the S phase DNA damage checkpoint results in S phase progression or premature mitosis depending on the concentration of 7-hydroxystaurosporine and the kinetics of Cdc25C activation
    Ethan A Kohn
    Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 277:26553-64. 2002
    ..Hence, UCN-01 has multiple effects depending on concentration and cell phenotype that must be considered when investigating mechanisms of checkpoint regulation...
  11. ncbi Cell cycle checkpoints and their impact on anticancer therapeutic strategies
    Alan Eastman
    Department of Pharmacology, and the Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Cell Biochem 91:223-31. 2004
    ..However, these defects also represent an Achilles heel that can be targeted to improve current therapeutic strategies...
  12. ncbi Distinct roles for p53 transactivation and repression in preventing UCN-01-mediated abrogation of DNA damage-induced arrest at S and G2 cell cycle checkpoints
    Aime A Levesque
    Department of Pharmacology and Toxicology, Dartmouth Medical School, Lebanon, NH 03756, USA
    Oncogene 24:3786-96. 2005
    ..These studies provide a mechanistic explanation for how this therapeutic strategy can selectively target tumor cells...
  13. ncbi The novel triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) potently enhances apoptosis induced by tumor necrosis factor in human leukemia cells
    Terrance A Stadheim
    Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 277:16448-55. 2002
    ....
  14. ncbi Conjugated linoleic acid (CLA) inhibits expression of the Spot 14 (THRSP) and fatty acid synthase genes and impairs the growth of human breast cancer and liposarcoma cells
    Christina Donnelly
    Department of Medicine, Section of Endocrinology and Metabolism, and the Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire, USA
    Nutr Cancer 61:114-22. 2009
    ..Rescue from the antiproliferative effect of CLA by palmitic acid indicates that reduced tumor lipogenesis is a major mechanism for the anticancer effects of CLA...
  15. ncbi p53-based cancer therapies: Is defective p53 the Achilles heel of the tumor?
    Aime A Levesque
    Department of Pharmacology and Toxicology, Dartmouth Medical School, Norris Cotton Cancer Center, One Medical Center Drive, Rubin Building Level 6, Lebanon, NH 03756, UK
    Carcinogenesis 28:13-20. 2007
    ..These contradictory approaches must be resolved if we are to take full advantage of the frequent p53 defect in tumors...
  16. ncbi Inhibition of either phosphatidylinositol 3-kinase/Akt or the mitogen/extracellular-regulated kinase, MEK/ERK, signaling pathways suppress growth of breast cancer cell lines, but MEK/ERK signaling is critical for cell survival
    Maureen O Ripple
    Department of Pharmacology and Toxicology, Dartmouth Medical School, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA
    Breast Cancer Res Treat 93:177-88. 2005
    ..Overall, the results demonstrate that the MEK/ERK pathway represents the more critical pathway for cell survival of these breast cancer cell lines, and suggest this pathways represents the better target for cancer therapy...
  17. ncbi High DNA methyltransferase 3B expression mediates 5-aza-deoxycytidine hypersensitivity in testicular germ cell tumors
    Maroun J Beyrouthy
    Department of Pharmacology, Dartmouth Medical School, Hanover, New Hamsphire 03755, USA
    Cancer Res 69:9360-6. 2009
    ..These novel findings indicate that high expression of DNMT3B, a likely byproduct of their pluripotency and germ cell origin, sensitizes TGCT-derived EC cells to low-dose 5-aza-CdR treatment...
  18. ncbi Vinblastine induces acute, cell cycle phase-independent apoptosis in some leukemias and lymphomas and can induce acute apoptosis in others when Mcl-1 is suppressed
    Bethany L Salerni
    Norris Cotton Cancer Center, Rubin Building Level 6, Dartmouth Medical School, Lebanon, NH 03756, USA
    Mol Cancer Ther 9:791-802. 2010
    ..These results suggest several clinical strategies that might provide an effective therapy for selected patients. Mol Cancer Ther; 9(4); 791-802. (c)2010 AACR...
  19. ncbi Inhibitors of protein phosphatases 1 and 2A differentially prevent intrinsic and extrinsic apoptosis pathways
    Kathryn Chatfield
    Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH 03756, USA
    Biochem Biophys Res Commun 323:1313-20. 2004
    ....
  20. ncbi Revised structure of the active form of human deoxyribonuclease IIalpha
    Kyle S MacLea
    Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Biochem Biophys Res Commun 292:415-21. 2002
    ..Similar results were obtained with overexpressed DNase IIalpha. These results suggest that active DNase IIalpha consists of one contiguous polypeptide. We suggest the previous structure reflects proteolysis during protein purification...
  21. ncbi Inducer-and cell type-specific regulation of antiapoptotic MCL1 in myeloid leukemia and multiple myeloma cells exposed to differentiation-inducing or microtubule-disrupting agents
    Julie A Vrana
    Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH 03755, USA
    Apoptosis 11:1275-88. 2006
    ..Thus, MCL1 expression level and sensitivity to regulation are important considerations in selecting approaches for targeting this antiapoptotic gene product to kill cancer cells...

Research Grants27

  1. CELL DEATH INDUCED BY ANTICANCER AGENTS
    Alan Eastman; Fiscal Year: 2004
    ..Finally, the applicant will attempt to reconstitute apoptosis in vitro to enable the potential regulators of endonucleases and apoptosis to be determined. ..
  2. CELL DEATH INDUCED BY ANTICANCER AGENTS
    Alan Eastman; Fiscal Year: 2007
    ..The ultimate goal of this research program will be to define which pathway and effector a specific leukemia uses, and then prescribe effective drug combinations that will be individualized for that patient. ..
  3. Mechanisms of Resistance to Cell Cycle Checkpoint Kinase Inhibitors
    Alan Eastman; Fiscal Year: 2007
    ..For those tumors in which a response is not indicated, these experiments will likely identify alternate targets for drug discovery. ..
  4. 2006 Molecular Therapeutics of Cancer Gordon Research Conference
    Alan Eastman; Fiscal Year: 2007
    ....
  5. Cancer Biology and Molecular Therapeutics
    Alan Eastman; Fiscal Year: 2007
    ..This new direction for the program was achieved in major part by the established track record of this training program, and as a consequence we are requesting continued support at the current level of training positions. ..
  6. Mechanisms of Resistance to Cell Cycle Checkpoint Kinase Inhibitors
    Alan Eastman; Fiscal Year: 2009
    ..For those tumors in which a response is not indicated, these experiments will likely identify alternate targets for drug discovery. ..
  7. Cell Survival Pathways and Inhibitors in Leukemia
    Alan Eastman; Fiscal Year: 2003
    ....
  8. CELL DEATH INDUCED BY ANTICANCER AGENTS
    Alan Eastman; Fiscal Year: 1993
    ..The outcome of these experiments may be the development of new strategies for drug development, for synergistic therapy, and for overcoming drug resistance...
  9. ABROGATION OF CELL CYCLE ARREST BY STAUROSPORINE ANALOGS
    Alan Eastman; Fiscal Year: 2001
    ..These experiments should identify a drug combination that can be tested for its selective targeting to p53-defective tumors in future clinical trials. ..
  10. Mechanisms of Resistance to Cell Cycle Checkpoint Kinase Inhibitors
    ALAN R EASTMAN; Fiscal Year: 2010
    ..For those tumors in which a response is not indicated, these experiments will likely identify alternate targets for drug discovery. ..