Geoffrey Shapiro

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint A phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer
    G I Shapiro
    Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Clin Cancer Res 7:1590-9. 2001
  2. doi request reprint Phase I studies of CBP501, a G2 checkpoint abrogator, as monotherapy and in combination with cisplatin in patients with advanced solid tumors
    Geoffrey I Shapiro
    Dana Farber Cancer Institute, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA
    Clin Cancer Res 17:3431-42. 2011
  3. ncbi request reprint Cyclin-dependent kinase pathways as targets for cancer treatment
    Geoffrey I Shapiro
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Clin Oncol 24:1770-83. 2006
  4. ncbi request reprint Preclinical and clinical development of the cyclin-dependent kinase inhibitor flavopiridol
    Geoffrey I Shapiro
    Department of Medical Oncology and Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Clin Cancer Res 10:4270s-4275s. 2004
  5. ncbi request reprint Selective sensitization of transformed cells to flavopiridol-induced apoptosis following recruitment to S-phase
    Christian B Matranga
    Department of Adult Oncology and Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Res 62:1707-17. 2002
  6. pmc Personalized tumor response assessment in the era of molecular medicine: cancer-specific and therapy-specific response criteria to complement pitfalls of RECIST
    Mizuki Nishino
    Department of Imaging, Dana Farber Cancer Institute, Boston, MA 02215, USA
    AJR Am J Roentgenol 198:737-45. 2012
  7. ncbi request reprint Flavopiridol-induced apoptosis during S phase requires E2F-1 and inhibition of cyclin A-dependent kinase activity
    Jingrui Jiang
    Department of Medical Oncology and Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Dana 810A, 44 Binney Street, Boston, MA 02115, USA
    Cancer Res 63:7410-22. 2003
  8. ncbi request reprint Allele-dependent variation in the relative cellular potency of distinct EGFR inhibitors
    Yuki Yuza
    Department of Medical Oncology, Center for Cancer Genome Discovery, Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Cancer Biol Ther 6:661-7. 2007
  9. ncbi request reprint Transcriptional profiling identifies cyclin D1 as a critical downstream effector of mutant epidermal growth factor receptor signaling
    Susumu Kobayashi
    Division of Hematology Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Cancer Res 66:11389-98. 2006
  10. ncbi request reprint Combined depletion of cell cycle and transcriptional cyclin-dependent kinase activities induces apoptosis in cancer cells
    Dongpo Cai
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cancer Res 66:9270-80. 2006

Research Grants

  1. Flavopiridol Mediated Apoptosis During S Phase in NSCLC
    Geoffrey Shapiro; Fiscal Year: 2003
  2. Flavopiridol Mediated Apoptosis During S Phase
    Geoffrey Shapiro; Fiscal Year: 2007
  3. Cyclin-Dependent Kinase Inhibition During S Phase
    Geoffrey I Shapiro; Fiscal Year: 2010

Detail Information

Publications28

  1. ncbi request reprint A phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer
    G I Shapiro
    Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Clin Cancer Res 7:1590-9. 2001
    ..A Phase II trial was conducted to determine the activity and toxicity of flavopiridol in untreated patients with metastatic NSCLC...
  2. doi request reprint Phase I studies of CBP501, a G2 checkpoint abrogator, as monotherapy and in combination with cisplatin in patients with advanced solid tumors
    Geoffrey I Shapiro
    Dana Farber Cancer Institute, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA
    Clin Cancer Res 17:3431-42. 2011
    ..Two phase I dose-escalation studies were conducted to determine the maximum tolerated dose (MTD) and safety profile of the G(2) checkpoint abrogator CBP501, as a single agent and in combination with cisplatin...
  3. ncbi request reprint Cyclin-dependent kinase pathways as targets for cancer treatment
    Geoffrey I Shapiro
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Clin Oncol 24:1770-83. 2006
    ..These efforts will establish whether the strategy of cdk inhibition is able to produce therapeutic benefit in the majority of human tumors...
  4. ncbi request reprint Preclinical and clinical development of the cyclin-dependent kinase inhibitor flavopiridol
    Geoffrey I Shapiro
    Department of Medical Oncology and Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Clin Cancer Res 10:4270s-4275s. 2004
    ..Loading followed by maintenance infusions are also under development, designed to achieve sustained micromolar drug levels. Clinical trials remain complicated by the absence of pharmacodynamic end points to confirm target inhibition...
  5. ncbi request reprint Selective sensitization of transformed cells to flavopiridol-induced apoptosis following recruitment to S-phase
    Christian B Matranga
    Department of Adult Oncology and Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Res 62:1707-17. 2002
    ..These data suggest that treatment during S-phase may maximize responses to flavopiridol and that the administration of flavopiridol after chemotherapy agents that cause S-phase accumulation may be an efficacious antitumor strategy...
  6. pmc Personalized tumor response assessment in the era of molecular medicine: cancer-specific and therapy-specific response criteria to complement pitfalls of RECIST
    Mizuki Nishino
    Department of Imaging, Dana Farber Cancer Institute, Boston, MA 02215, USA
    AJR Am J Roentgenol 198:737-45. 2012
    ....
  7. ncbi request reprint Flavopiridol-induced apoptosis during S phase requires E2F-1 and inhibition of cyclin A-dependent kinase activity
    Jingrui Jiang
    Department of Medical Oncology and Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Dana 810A, 44 Binney Street, Boston, MA 02115, USA
    Cancer Res 63:7410-22. 2003
    ....
  8. ncbi request reprint Allele-dependent variation in the relative cellular potency of distinct EGFR inhibitors
    Yuki Yuza
    Department of Medical Oncology, Center for Cancer Genome Discovery, Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Cancer Biol Ther 6:661-7. 2007
    ..More broadly, these results imply that the development and deployment of targeted therapies should focus on inhibition of specific cancer-causing mutations, not only on the mutated target...
  9. ncbi request reprint Transcriptional profiling identifies cyclin D1 as a critical downstream effector of mutant epidermal growth factor receptor signaling
    Susumu Kobayashi
    Division of Hematology Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
    Cancer Res 66:11389-98. 2006
    ..These studies suggest that cyclin D1 may contribute to the emergence of EGFR-driven tumorigenesis and can be an alternative target of therapy...
  10. ncbi request reprint Combined depletion of cell cycle and transcriptional cyclin-dependent kinase activities induces apoptosis in cancer cells
    Dongpo Cai
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cancer Res 66:9270-80. 2006
    ..These results show the potency of concomitant compromise of cell cycle and transcriptional cdk activities and may guide the selection of clinical drug candidates...
  11. ncbi request reprint Modulation of the c-Met/hepatocyte growth factor pathway in small cell lung cancer
    Gautam Maulik
    Department of Adult Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Clin Cancer Res 8:620-7. 2002
    ..These results demonstrate that c-Met/HGF pathway is functional in SCLC, and it would be useful to target this pathway toward novel therapy...
  12. ncbi request reprint Phase I trial of the matrix metalloproteinase inhibitor marimastat combined with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer
    John R Goffin
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Clin Cancer Res 11:3417-24. 2005
    ..A phase I study was initiated to determine whether conventional doses of carboplatin and paclitaxel are tolerated when combined with marimastat and to assess the influence of marimastat on paclitaxel pharmacokinetics...
  13. ncbi request reprint Bioluminescent imaging of Cdk2 inhibition in vivo
    Guo Jun Zhang
    Department of Adult Oncology, Dana Farber Cancer Institute and Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Med 10:643-8. 2004
    ..In theory, the approach described here could be used to develop bioluminescent reporters for any drug target that directly or indirectly affects the turnover of a ubiquitin ligase substrate...
  14. ncbi request reprint AZ703, an imidazo[1,2-a]pyridine inhibitor of cyclin-dependent kinases 1 and 2, induces E2F-1-dependent apoptosis enhanced by depletion of cyclin-dependent kinase 9
    Dongpo Cai
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cancer Res 66:435-44. 2006
    ....
  15. ncbi request reprint Flavopiridol reduces malignant transformation of the esophageal mucosa in p27 knockout mice
    Mirna Lechpammer
    Department of Medical Oncology, Dana Farber Cancer Institute, D740 44 Binney Street, Boston, MA 02115, USA
    Oncogene 24:1683-8. 2005
    ..The results of this study represent the experimental basis for chemoprevention with cdk inhibitors in human BE and BAA...
  16. doi request reprint A phase I study of foretinib, a multi-targeted inhibitor of c-Met and vascular endothelial growth factor receptor 2
    Joseph Paul Eder
    Early Drug Development Center, Department of Medical Oncology, Dana Farber Cancer Institute and Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Clin Cancer Res 16:3507-16. 2010
    ..Secondary objectives included evaluation of plasma pharmacokinetics, long-term safety after repeated administration, preliminary antitumor activity, and pharmacodynamic activity...
  17. pmc Integrative genomic and proteomic analyses identify targets for Lkb1-deficient metastatic lung tumors
    Julian Carretero
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115 USA
    Cancer Cell 17:547-59. 2010
    ..These studies demonstrate that integrated genomic and proteomic analyses can be used to identify signaling pathways that may be targeted for treatment...
  18. pmc Pattern of retinoblastoma pathway inactivation dictates response to CDK4/6 inhibition in GBM
    W Ruprecht Wiedemeyer
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:11501-6. 2010
    ..More generally, these observations demonstrate that the integration of genomic, functional and pharmacologic data can be exploited to inform the development of targeted therapy directed against specific cancer pathways...
  19. doi request reprint Development of phosphoinositide-3 kinase pathway inhibitors for advanced cancer
    James M Cleary
    Department of Medical Oncology, Early Drug Development Center, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA, 02115, USA
    Curr Oncol Rep 12:87-94. 2010
    ..This article reviews preclinical and clinical data on members of this novel drug class, as well as data justifying the combination of PI3K inhibitors with other anticancer agents...
  20. doi request reprint Phase I study of the c-raf-1 antisense oligonucleotide ISIS 5132 in combination with carboplatin and paclitaxel in patients with previously untreated, advanced non-small cell lung cancer
    Panos Fidias
    Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    J Thorac Oncol 4:1156-62. 2009
    ....
  21. doi request reprint A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors
    Kwok K Wong
    Dana Farber Cancer Institute, and Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Clin Cancer Res 15:2552-8. 2009
    ..The dose-limiting toxicities, maximum tolerated dose, pharmacokinetic profile, and preliminary antitumor activity of neratinib (HKI-272), an irreversible pan ErbB inhibitor, were determined in patients with advanced solid tumors...
  22. pmc HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy
    Samanthi A Perera
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 106:474-9. 2009
    ..Based on these findings, clinical testing of the BIBW2992/rapamycin combination in non-small cell lung cancer patients with tumors expressing HER2 mutations is warranted...
  23. pmc Hsp90 inhibition suppresses mutant EGFR-T790M signaling and overcomes kinase inhibitor resistance
    Takeshi Shimamura
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02215, USA
    Cancer Res 68:5827-38. 2008
    ..Nonetheless, these findings suggest that Hsp90 inhibitors may be effective in T790M-expressing cells and offer an alternative therapeutic strategy for this subset of lung cancers...
  24. ncbi request reprint A phase II clinical and pharmacodynamic study of E7070 in patients with metastatic, recurrent, or refractory squamous cell carcinoma of the head and neck: modulation of retinoblastoma protein phosphorylation by a novel chloroindolyl sulfonamide cell cycle
    Robert I Haddad
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Clin Cancer Res 10:4680-7. 2004
    ..This Phase II study was conducted to explore the efficacy, safety, and pharmacodynamics of E7070 in squamous cell carcinoma of the head and neck (SCCHN)...
  25. doi request reprint Summary statement novel agents in the treatment of lung cancer: Fifth Cambridge Conference assessing opportunities for combination therapy
    Thomas J Lynch
    Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA
    J Thorac Oncol 3:S107-12. 2008
    ..A CME activity based on this summary is also available at www.informedicalcme.com/cme...
  26. ncbi request reprint Bronchial and peripheral murine lung carcinomas induced by T790M-L858R mutant EGFR respond to HKI-272 and rapamycin combination therapy
    Danan Li
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cancer Cell 12:81-93. 2007
    ..However, the combination of HKI-272 and rapamycin resulted in significant regression of both types of lung tumors. This combination therapy may potentially benefit lung cancer patients with the EGFR T790M mutation...
  27. ncbi request reprint The Aurora kinase inhibitor VX-680 induces endoreduplication and apoptosis preferentially in cells with compromised p53-dependent postmitotic checkpoint function
    Farid Gizatullin
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Cancer Res 66:7668-77. 2006
    ..Although cells with intact checkpoint function arrest with 4N DNA content, those with compromised checkpoint function are more likely to undergo endoreduplication followed by eventual apoptosis...
  28. doi request reprint Phase I study of flavopiridol in combination with Paclitaxel and Carboplatin in patients with non-small-cell lung cancer
    Saby George
    Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Clin Lung Cancer 9:160-5. 2008
    ....

Research Grants9

  1. Flavopiridol Mediated Apoptosis During S Phase in NSCLC
    Geoffrey Shapiro; Fiscal Year: 2003
    ..In vitro studies will be performed to determine whether flavopiridol affects the metabolism of gemcitabine. The pharmacokinetic interactions of the two drugs in patients will also be explored. ..
  2. Flavopiridol Mediated Apoptosis During S Phase
    Geoffrey Shapiro; Fiscal Year: 2007
    ..In addition to pharmacokinetic analyses, the trial will incorporate pharmacodynamic endpoints for flavopiridol activity in tumor tissue, skin and plasma. ..
  3. Cyclin-Dependent Kinase Inhibition During S Phase
    Geoffrey I Shapiro; Fiscal Year: 2010
    ..Preclinical work will justify clinical trials both of cdk inhibitors used alone and in concert with DNA damage, representing novel anti-cancer strategies. ..