Keith T Flaherty

Summary

Publications

  1. pmc Phase II trial of sorafenib in advanced thyroid cancer
    Vandana Gupta-Abramson
    Developmental TherapeuticsProgram of the Abramson CancerCenter, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Clin Oncol 26:4714-9. 2008
  2. pmc Future perspectives in melanoma research. Meeting report from the "Melanoma research: a bridge from Naples to the World. Napoli, December 5th-6th 2011"
    Paolo A Ascierto
    Department of Melanoma, Sarcoma, and Head and Neck Disease, Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy
    J Transl Med 10:83. 2012
  3. pmc Future perspectives in melanoma research. Meeting report from the "Melanoma Research: a bridge Naples-USA. Naples, December 6th-7th 2010"
    Paolo A Ascierto
    Department of Melanoma, Sarcoma, and Head and Neck Disease, Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy
    J Transl Med 9:32. 2011
  4. ncbi Antisense therapeutics: lessons from early clinical trials
    K T Flaherty
    University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania 19104, USA
    Curr Opin Oncol 13:499-505. 2001
  5. ncbi Pilot study of DCE-MRI to predict progression-free survival with sorafenib therapy in renal cell carcinoma
    Keith T Flaherty
    Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cancer Biol Ther 7:496-501. 2008
  6. ncbi Sorafenib: delivering a targeted drug to the right targets
    Keith T Flaherty
    University of Pennsylvania, Abramson Cancer Center, PA 19104, USA
    Expert Rev Anticancer Ther 7:617-26. 2007
  7. ncbi A phase I trial of the oral, multikinase inhibitor sorafenib in combination with carboplatin and paclitaxel
    Keith T Flaherty
    The Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Clin Cancer Res 14:4836-42. 2008
  8. ncbi The future of tyrosine kinase inhibitors: single agent or combination?
    Keith T Flaherty
    Abramson Cancer Center, University of Pennsylvania, 12 Penn Tower, 3400 Spruce Street, Philadelphia, PA 19104, USA
    Curr Oncol Rep 10:264-70. 2008
  9. doi BRAF, a target in melanoma: implications for solid tumor drug development
    Keith T Flaherty
    Division of Hematology Oncology, Massuchusetts General Hospital Cancer Center, Boston, Massachusetts, USA
    Cancer 116:4902-13. 2010
  10. ncbi Chemotherapy and targeted therapy combinations in advanced melanoma
    Keith T Flaherty
    Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Clin Cancer Res 12:2366s-2370s. 2006

Research Grants

Detail Information

Publications79

  1. pmc Phase II trial of sorafenib in advanced thyroid cancer
    Vandana Gupta-Abramson
    Developmental TherapeuticsProgram of the Abramson CancerCenter, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Clin Oncol 26:4714-9. 2008
    ....
  2. pmc Future perspectives in melanoma research. Meeting report from the "Melanoma research: a bridge from Naples to the World. Napoli, December 5th-6th 2011"
    Paolo A Ascierto
    Department of Melanoma, Sarcoma, and Head and Neck Disease, Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy
    J Transl Med 10:83. 2012
    ....
  3. pmc Future perspectives in melanoma research. Meeting report from the "Melanoma Research: a bridge Naples-USA. Naples, December 6th-7th 2010"
    Paolo A Ascierto
    Department of Melanoma, Sarcoma, and Head and Neck Disease, Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy
    J Transl Med 9:32. 2011
    ..Four topics of discussion were identified: New pathways in Melanoma, Biomarkers, Clinical Trials and New Molecules and Strategies...
  4. ncbi Antisense therapeutics: lessons from early clinical trials
    K T Flaherty
    University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania 19104, USA
    Curr Opin Oncol 13:499-505. 2001
    ..Antisense oligodeoxynucleotides against bcl-2, c-raf-1, and protein kinase C-alpha continue to be the focus of ongoing trials...
  5. ncbi Pilot study of DCE-MRI to predict progression-free survival with sorafenib therapy in renal cell carcinoma
    Keith T Flaherty
    Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cancer Biol Ther 7:496-501. 2008
    ..Sorafenib is a novel RAF and VEGF receptor tyrosine kinase inhibitor. We conducted this study to (a) determine if sorafenib is anti-angiogenic, and (b) to relate anti-angiogenic effect to outcome...
  6. ncbi Sorafenib: delivering a targeted drug to the right targets
    Keith T Flaherty
    University of Pennsylvania, Abramson Cancer Center, PA 19104, USA
    Expert Rev Anticancer Ther 7:617-26. 2007
    ..A detailed discussion of the clinical trials in renal cell carcinoma, melanoma and hepatocellular carcinoma highlights what is known and what has yet to be understood about this agent...
  7. ncbi A phase I trial of the oral, multikinase inhibitor sorafenib in combination with carboplatin and paclitaxel
    Keith T Flaherty
    The Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Clin Cancer Res 14:4836-42. 2008
    ..This study evaluated the safety, maximum tolerated dose, pharmacokinetics, and antitumor activity of sorafenib, a multikinase inhibitor, combined with paclitaxel and carboplatin in patients with solid tumors...
  8. ncbi The future of tyrosine kinase inhibitors: single agent or combination?
    Keith T Flaherty
    Abramson Cancer Center, University of Pennsylvania, 12 Penn Tower, 3400 Spruce Street, Philadelphia, PA 19104, USA
    Curr Oncol Rep 10:264-70. 2008
    ..A careful consideration of the specific mechanism of action of each agent provides a basis for considering the optimal therapeutic strategies for incorporating each of these agents into the management of metastatic RCC...
  9. doi BRAF, a target in melanoma: implications for solid tumor drug development
    Keith T Flaherty
    Division of Hematology Oncology, Massuchusetts General Hospital Cancer Center, Boston, Massachusetts, USA
    Cancer 116:4902-13. 2010
    ..The current investigations in melanoma will create a set of hypotheses to be tested in each cancer that harbors BRAF mutations...
  10. ncbi Chemotherapy and targeted therapy combinations in advanced melanoma
    Keith T Flaherty
    Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Clin Cancer Res 12:2366s-2370s. 2006
    ..The mechanism by which signaling inhibition might synergize with chemotherapy requires more study so that rational combinations move forward. Very few targeted agents have been studied rigorously in this fashion...
  11. ncbi Sorafenib in renal cell carcinoma
    Keith T Flaherty
    Abramson Cancer Center, University of Pennsylvania, 51 North 39th Street, Philadelphia, PA 19104, USA
    Clin Cancer Res 13:747s-752s. 2007
    ..Preliminary evidence with this approach is promising and will be the subject of the next generation of randomized trials in renal cell carcinoma...
  12. ncbi Dose escalation study of tezacitabine in combination with cisplatin in patients with advanced cancer
    Keith T Flaherty
    Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cancer 97:1985-90. 2003
    ..The authors performed a dose escalation study of cisplatin and the novel deoxycytidine analog, tezacitabine, to determine the maximum tolerated dose of the combination...
  13. ncbi New molecular targets in melanoma
    Keith T Flaherty
    Instructor of Medicine, Abramson Cancer Center of the University of Pennsylvania, 51 N 39th Street, MAB 103, Philadelphia, PA 19104, USA
    Curr Opin Oncol 16:150-4. 2004
    ..Therapies that target the molecular pathophysiology of metastatic melanoma provide hope that more effective treatments will soon be available...
  14. ncbi A phase I, dose escalation trial of ZD0473, a novel platinum analogue, in combination with gemcitabine
    Keith T Flaherty
    Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA 19104, USA
    Cancer Chemother Pharmacol 53:404-8. 2004
    ..In single-agent studies of ZD0473, myelosuppression was the predominant toxicity and responses wer observed...
  15. pmc BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma
    Dennie T Frederick
    Division of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Clin Cancer Res 19:1225-31. 2013
    ..To evaluate the effects of BRAF inhibition on the tumor microenvironment in patients with metastatic melanoma...
  16. doi Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study
    Keith T Flaherty
    Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA
    Cancer Chemother Pharmacol 68:1111-8. 2011
    ....
  17. ncbi Cell cycle dependent and schedule-dependent antitumor effects of sorafenib combined with radiation
    John P Plastaras
    Laboratory of Molecular Oncology and Cell Cycle Regulation, Department of Medicine Hematology Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Cancer Res 67:9443-54. 2007
    ..This study establishes a foundation for clinical testing of sequential fractionated radiation followed by sorafenib in gastrointestinal and other malignancies...
  18. ncbi Phase I trial of combretastatin a-4 phosphate with carboplatin
    Joshua H Bilenker
    University of Pennsylvania Cancer Center, University of the Sciences in Philadelphia, Philadelphia, PA 19104, USA
    Clin Cancer Res 11:1527-33. 2005
    ..Preclinical evidence of synergy led to a phase I trial employing combretastatin A-4 phosphate (CA4P), a novel tubulin-binding antivascular drug, in combination with carboplatin...
  19. doi MRI assessment of early tumor response in metastatic renal cell carcinoma patients treated with sorafenib
    Hyunseon Christine Kang
    Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
    AJR Am J Roentgenol 200:120-6. 2013
    ..The purpose of this study was to examine early MRI changes in renal cell carcinoma (RCC) treated with the antiangiogenic agent sorafenib and to identify MRI biomarkers of RCC response to sorafenib...
  20. doi Resistance to BRAF-targeted therapy in melanoma
    Ryan J Sullivan
    Center for Melanoma Massachusetts General Hospital Cancer Center 55 Fruit Street, Boston, MA 02114, USA
    Eur J Cancer 49:1297-304. 2013
    ....
  21. doi Photodynamic therapy for multiple eruptive keratoacanthomas associated with vemurafenib treatment for metastatic melanoma
    Allireza Alloo
    Department of Dermatology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Arch Dermatol 148:363-6. 2012
    ..With multiple such neoplasms often arising after BRAF inhibitor therapy, surgical excision is often impractical...
  22. doi Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lymphocyte function
    Andrea Boni
    Division of Surgical Oncology, Medical Oncology, and Dermatology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Cancer Res 70:5213-9. 2010
    ..These findings have important implications for combined kinase-targeted therapy plus immunotherapy for melanoma...
  23. ncbi Phase III trial of carboplatin and paclitaxel with or without sorafenib in metastatic melanoma
    Keith T Flaherty
    Massachusetts General Hospital, 55 Fruit St, Yawkey 9E, Boston, MA 02114, USA
    J Clin Oncol 31:373-9. 2013
    ..The primary objective of this study was to determine whether carboplatin, paclitaxel, and sorafenib (CPS) improve overall survival (OS) compared with carboplatin and paclitaxel (CP) in chemotherapy-naive patients with metastatic melanoma...
  24. ncbi Mechanisms of hypertension associated with BAY 43-9006
    Maria Luisa Veronese
    Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Clin Oncol 24:1363-9. 2006
    ..The current study investigated the incidence, severity, and mechanism of blood pressure (BP) elevation in patients treated with BAY 43-9006...
  25. pmc Identification of a novel subgroup of melanomas with KIT/cyclin-dependent kinase-4 overexpression
    Keiran S M Smalley
    The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
    Cancer Res 68:5743-52. 2008
    ..This group of melanomas may be a subpopulation for which imatinib or other KIT inhibitors may constitute optimal therapy...
  26. ncbi Outcomes of patients with metastatic melanoma treated with immunotherapy prior to or after BRAF inhibitors
    Allison Ackerman
    Department of Medicine, Division of Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
    Cancer 120:1695-701. 2014
    ..This retrospective analysis describes the outcomes of patients treated with either BRAFi before IT or IT before BRAFi...
  27. pmc TORC1 suppression predicts responsiveness to RAF and MEK inhibition in BRAF-mutant melanoma
    Ryan B Corcoran
    Massachusetts General Hospital Cancer Center, Boston, MA 02129, USA
    Sci Transl Med 5:196ra98. 2013
    ..Such a change in P-S6 could be readily monitored in real time by serial fine-needle aspiration biopsies, making quantitation of P-S6 a valuable biomarker to guide treatment in BRAF-mutant melanoma. ..
  28. pmc Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations
    Keith T Flaherty
    Massachusetts General Hospital Cancer Center, Boston, USA
    N Engl J Med 367:1694-703. 2012
    ..To address this problem, we conducted a phase 1 and 2 trial of combined treatment with dabrafenib, a selective BRAF inhibitor, and trametinib, a selective MAPK kinase (MEK) inhibitor...
  29. ncbi Phase I, dose-escalation trial of the oral cyclin-dependent kinase 4/6 inhibitor PD 0332991, administered using a 21-day schedule in patients with advanced cancer
    Keith T Flaherty
    Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA
    Clin Cancer Res 18:568-76. 2012
    ....
  30. ncbi Drug targeting of oncogenic pathways in melanoma
    Leslie A Fecher
    Department of Medicine, Division of Hematology and Oncology, Abramson Cancer Center, University of Pennsylvania, 3400 Spruce Street, 16 Penn Tower, Philadelphia, PA 19104, USA
    Hematol Oncol Clin North Am 23:599-618, x. 2009
    ..The targeting of certain cellular processes, downstream of the common genetic alterations, for which the issues of target and drug validation are somewhat distinct, are also highlighted...
  31. pmc Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas
    Keiran S M Smalley
    The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
    Mol Cancer Ther 7:2876-83. 2008
    ....
  32. pmc Hypoxia induces phenotypic plasticity and therapy resistance in melanoma via the tyrosine kinase receptors ROR1 and ROR2
    Michael P O'Connell
    1Tumor Metastasis and Microenvironment Program and 2Molecular and Cellular Oncogenesis Program, The Wistar Institute 3Abramson Cancer Center, University of Pennsylvania, Philadelphia 4Lehigh Valley Health Network, Allentown, Pennsylvania 5The National Institute on Aging, NIH, Baltimore, Maryland and 6Dana Farber Harvard Cancer Center, Boston, Massachusetts
    Cancer Discov 3:1378-93. 2013
    ..These data highlight the fact that mechanisms that guide metastatic progression may be linked to those that mediate therapy resistance...
  33. ncbi Phase I combination trial of gemcitabine, paclitaxel, and carboplatin in patients with advanced malignancy
    Keith T Flaherty
    Abramson Cancer Center, University of Pennsylvania, Medical Arts Buildingm Suite 103, 39th and Market Streets, Philadelphia, PA 19104, USA
    Cancer Chemother Pharmacol 52:217-22. 2003
    ..We performed a phase I trial of carboplatin and paclitaxel in combination with gemcitabine in order to determine the tolerability of this triplet...
  34. pmc Two phase 2 trials of the novel Akt inhibitor perifosine in patients with advanced renal cell carcinoma after progression on vascular endothelial growth factor-targeted therapy
    Daniel C Cho
    Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
    Cancer 118:6055-62. 2012
    ....
  35. doi p53 rescue through HDM2 antagonism suppresses melanoma growth and potentiates MEK inhibition
    Zhenyu Ji
    Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    J Invest Dermatol 132:356-64. 2012
    ..These results provide fundamental insights into the intact p53 circuitry, which can be restored through small molecule inhibitors and potentially deployed for therapeutic gain...
  36. ncbi Multiple signaling pathways must be targeted to overcome drug resistance in cell lines derived from melanoma metastases
    Keiran S M Smalley
    The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
    Mol Cancer Ther 5:1136-44. 2006
    ..It is further suggested that BRAF mutational status is not predictive of response to MEK inhibition under three-dimensional culture conditions...
  37. pmc HIF-alpha effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma
    John D Gordan
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cancer Cell 14:435-46. 2008
    ..These reproducible distinctions in ccRCC behavior delineate HIF-alpha effects on c-Myc in vivo and suggest molecular criteria for selecting targeted therapies...
  38. ncbi Phase 1 and pharmacodynamic trial of everolimus in combination with cetuximab in patients with advanced cancer
    Christine A Ciunci
    Abramson Cancer Center, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
    Cancer 120:77-85. 2014
    ..Therefore, a phase 1/pharmacodynamic trial of everolimus with cetuximab was performed...
  39. pmc Clinical activity of ipilimumab for metastatic uveal melanoma: a retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience
    Jason J Luke
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts
    Cancer 119:3687-95. 2013
    ....
  40. ncbi Phase I trial of the antifolate ZD9331 in combination with cisplatin in patients with refractory solid malignancies
    Joshua H Bilenker
    Abramson Family Cancer Center, University of Pennsylvania, Philadelphia, PA, USA
    Cancer Chemother Pharmacol 53:357-60. 2004
    ..To determine the maximum tolerated dose and dose-limiting toxicities (DLTs) of ZD9331 in combination with cisplatin in patients with refractory solid tumors and to describe any preliminary antitumor activity associated with this regimen...
  41. pmc EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib
    Ryan B Corcoran
    Massachusetts General Hospital Cancer Center, Boston, MA 02129, USA
    Cancer Discov 2:227-35. 2012
    ..These findings support evaluation of combined RAF and EGFR inhibition in BRAF mutant CRC patients...
  42. pmc New challenges in endpoints for drug development in advanced melanoma
    Antoni Ribas
    Department of Medicine, Division of Hematology Oncology, University of California Los Angeles, CA90095, USA
    Clin Cancer Res 18:336-41. 2012
    ....
  43. ncbi Where are we with adjuvant therapy of stage III and IV melanoma in 2009?
    Leslie A Fecher
    Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
    J Natl Compr Canc Netw 7:295-304. 2009
    ..This article explores the factors to consider when individualizing care within the scope of these guidelines...
  44. ncbi Surrogate endpoints for overall survival in metastatic melanoma: a meta-analysis of randomised controlled trials
    Keith T Flaherty
    Center for Melanoma, Massachusetts General Hospital Cancer Center, Boston, MA, USA
    Lancet Oncol 15:297-304. 2014
    ..We aimed to assess whether progression-free survival (PFS) could be regarded as a reliable surrogate for overall survival through a meta-analysis of randomised trials...
  45. ncbi A melanocyte lineage program confers resistance to MAP kinase pathway inhibition
    Cory M Johannessen
    1 The Broad Institute of Harvard University and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA 2 Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA 3 Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA
    Nature 504:138-42. 2013
    ..Collectively, these data suggest that oncogenic dysregulation of a melanocyte lineage dependency can cause resistance to RAF-MEK-ERK inhibition, which may be overcome by combining signalling- and chromatin-directed therapeutics. ..
  46. doi Dividing and conquering: controlling advanced melanoma by targeting oncogene-defined subsets
    Keith T Flaherty
    Massachusetts General Hospital Cancer Center, Harvard Medical School, 55 Fruit St, Yawkey 9E, Boston, MA 02114, USA
    Clin Exp Metastasis 29:841-6. 2012
    ....
  47. ncbi Innovations and challenges in renal cell carcinoma: summary statement from the Second Cambridge Conference
    Michael B Atkins
    Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA
    Clin Cancer Res 13:667s-670s. 2007
    ....
  48. ncbi Clinical activity and immune modulation in cancer patients treated with CP-870,893, a novel CD40 agonist monoclonal antibody
    Robert H Vonderheide
    Abramson Family Cancer Research Institute, Abramson Cancer Center, Division of Hematology Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    J Clin Oncol 25:876-83. 2007
    ..CD40 is also expressed by solid tumors, but its engagement results in apoptosis. CP-870,893, a fully human and selective CD40 agonist monoclonal antibody (mAb), was tested for safety in a phase I dose-escalation study...
  49. pmc Inhibition of mutated, activated BRAF in metastatic melanoma
    Keith T Flaherty
    Abramson Cancer Center of the University of Pennsylvania, Philadelphia, USA
    N Engl J Med 363:809-19. 2010
    ..The identification of somatic mutations in the gene encoding the serine-threonine protein kinase B-RAF (BRAF) in the majority of melanomas offers an opportunity to test oncogene-targeted therapy for this disease...
  50. ncbi CRM1 and BRAF inhibition synergize and induce tumor regression in BRAF-mutant melanoma
    Roberto A Salas Fragomeni
    Harvard Medical School, Boston, MA, USA
    Mol Cancer Ther 12:1171-9. 2013
    ..In conclusion, CRM1 inhibition impairs melanoma survival in both BRAF-mutant and wild-type melanoma. The combination of CRM1 and BRAF inhibition synergizes and induces melanoma regression in BRAF-mutant melanoma...
  51. doi Detection of novel actionable genetic changes in salivary duct carcinoma helps direct patient treatment
    Valentina Nardi
    Departments of Pathology and Medicine, Massachusetts General Hospital Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA
    Clin Cancer Res 19:480-90. 2013
    ..We investigated whether genotyping analysis could detect novel tumor-specific mutations that would help direct SDC patient treatment using targeted agents...
  52. doi MEK and RAF inhibitors for BRAF-mutated cancers
    Sarah Belden
    Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA
    Expert Rev Mol Med 14:e17. 2012
    ....
  53. doi From genes to drugs: targeted strategies for melanoma
    Keith T Flaherty
    Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, Massachusetts 02114, USA
    Nat Rev Cancer 12:349-61. 2012
    ..This Review focuses on these recent striking advances in the strategy of molecularly targeted approaches to the therapy of melanoma in humans...
  54. doi Improved survival with MEK inhibition in BRAF-mutated melanoma
    Keith T Flaherty
    Massachusetts General Hospital Cancer Center, Boston, USA
    N Engl J Med 367:107-14. 2012
    ..Selective BRAF-inhibitor therapy improves survival, as compared with chemotherapy, but responses are often short-lived. In previous trials, MEK inhibition appeared to be promising in this population...
  55. doi Targeting metastatic melanoma
    Keith T Flaherty
    Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts 02114, USA
    Annu Rev Med 63:171-83. 2012
    ..Ongoing translational research seeks to identify the most scientifically rational combination treatment strategies to build on single-agent targeted therapy...
  56. pmc Targeting the RAS pathway in melanoma
    Zhenyu Ji
    Wellman Center for Photomedicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
    Trends Mol Med 18:27-35. 2012
    ..In this review, the current state of targeted therapy for melanoma is discussed, including the potent BRAF(V600E) inhibitor vemurafenib...
  57. ncbi An organometallic protein kinase inhibitor pharmacologically activates p53 and induces apoptosis in human melanoma cells
    Keiran S M Smalley
    The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA
    Cancer Res 67:209-17. 2007
    ..Taken together, our data provide a new strategy for the pharmacologic activation of p53 in melanoma, which may be a viable approach for overcoming apoptotic resistance in melanoma and offer new hope for rational melanoma therapy...
  58. doi Narrative review: BRAF opens the door for therapeutic advances in melanoma
    Keith T Flaherty
    Massachusetts General Hospital Cancer Center, Boston, 02114, USA
    Ann Intern Med 153:587-91. 2010
    ..Clinicians should be aware of phase 3 trials of these agents and trials combining these therapies with other novel therapies because, at a minimum, BRAF inhibitors seem to be valuable as palliative therapy for metastatic melanoma...
  59. doi BRAF targeted therapy changes the treatment paradigm in melanoma
    Antoni Ribas
    Department of Medicine, Division of Hematology Oncology, University of California Los Angeles, and Jonsson Comprehensive Cancer Center at UCLA, 11 934 Factor Building, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA
    Nat Rev Clin Oncol 8:426-33. 2011
    ..Vemurafenib (PLX4032) and GSK2118436, two orally available and well tolerated agents are on the verge of transforming the landscape of melanoma therapy based on the promising results of their respective phase I, II, and III trials...
  60. ncbi Is ERK activation a good biomarker for estradiol and tamoxifen effects?
    Keiran S M Smalley
    Wistar Institute, Philadelphia, Pennsylvania, USA
    Cancer Biol Ther 6:119-20. 2007
  61. ncbi Her-2 targeted therapy: beyond breast cancer and trastuzumab
    Keith T Flaherty
    Abramson Cancer Center of the University of Pennsylvania, 51 N 39th Street, MAB 103, Philadelphia, PA 19104, USA
    Curr Oncol Rep 8:90-5. 2006
    ..Preliminary results from early clinical trials suggest that Her-2 tyrosine kinase inhibitors may extend the population for which this strategy offers therapeutic effect...
  62. ncbi The MAPK pathway in melanoma
    Leslie A Fecher
    University of Pennsylvania, Division of Hematology and Oncology, Department of Medicine, The Abramson Cancer Center, Philadelphia, Pennsylvania 19104, USA
    Curr Opin Oncol 20:183-9. 2008
    ..Several therapeutic agents directed against this pathway are in development. This review summarizes current understanding of the MAPK pathway in melanoma biology and therapeutic strategies...
  63. ncbi Targeted therapy for metastatic melanoma
    Ravi K Amaravadi
    Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA
    Clin Adv Hematol Oncol 5:386-94. 2007
  64. pmc The anti-melanoma activity of dinaciclib, a cyclin-dependent kinase inhibitor, is dependent on p53 signaling
    Brijal M Desai
    The Wistar Institute, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 8:e59588. 2013
    ..Altogether, these data show that dinaciclib induces apoptosis in a large panel of melanoma cell lines through a mechanism requiring p53 expression...
  65. pmc Oncogenic NRAS signaling differentially regulates survival and proliferation in melanoma
    Lawrence N Kwong
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
    Nat Med 18:1503-10. 2012
    ..Such a gated signaling model offers a new framework to identify nonobvious coextinction target(s) for combined pharmacological inhibition in NRAS-mutant melanomas...
  66. doi BRAF inhibitors and melanoma
    Keith T Flaherty
    Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA
    Cancer J 17:505-11. 2011
    ..Opportunities for combining BRAF inhibitors with other signal transduction inhibitors as well as targeted therapies with distinct mechanisms of action are discussed...
  67. ncbi Reduction of TRAIL-induced Mcl-1 and cIAP2 by c-Myc or sorafenib sensitizes resistant human cancer cells to TRAIL-induced death
    M Stacey Ricci
    Laboratory of Molecular Oncology and Cell Cycle Regulation, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cancer Cell 12:66-80. 2007
    ..Combining sorafenib with TRAIL in vivo showed dramatic efficacy in TRAIL-resistant tumor xenografts. We propose the combination of TRAIL with sorafenib holds promise for further development...
  68. doi Molecular therapeutic approaches to melanoma
    Zhenyu Ji
    Wellman Center for Photomedicine Dept of Dermatology, 55 Fruit Street, Boston, MA 02114, USA
    Mol Aspects Med 31:194-204. 2010
    ....
  69. ncbi VEGFR-targeted therapy
    Keith T Flaherty
    Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA
    Clin Adv Hematol Oncol 3:371-2. 2005
  70. doi New strategies in metastatic melanoma: oncogene-defined taxonomy leads to therapeutic advances
    Keith T Flaherty
    Massachusetts General Hospital Cancer Center, Boston, MA 02129, USA
    Clin Cancer Res 17:4922-8. 2011
    ..The melanoma field stands poised to take the lead among cancer subtypes in advancing combination therapy strategies that simultaneously target multiple biologic underpinnings of the disease...
  71. pmc Collapse of the CD27+ B-cell compartment associated with systemic plasmacytosis in patients with advanced melanoma and other cancers
    Erica L Carpenter
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Clin Cancer Res 15:4277-87. 2009
    ..This study aimed to investigate whether B-cell physiology was altered in the presence of melanoma and other cancers...
  72. ncbi Innovations and challenges in melanoma: summary statement from the first Cambridge conference
    Michael B Atkins
    Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    Clin Cancer Res 12:2291s-2296s. 2006
    ....
  73. ncbi HIV protease inhibitor nelfinavir inhibits growth of human melanoma cells by induction of cell cycle arrest
    Wei Jiang
    Division of Endocrine and Oncologic Surgery, Department of Surgery, University of Pennsylvania Medical Center, 4 Silverstein, 3400 Spruce Street, Philadelphia, PA 19104, USA
    Cancer Res 67:1221-7. 2007
    ..Our results suggest that nelfinavir is a promising candidate chemotherapeutic agent for advanced melanoma, for which novel and effective therapies are urgently needed...
  74. ncbi A prospective study of body mass index, hypertension, and smoking and the risk of renal cell carcinoma (United States)
    Keith T Flaherty
    Department of Medicine, Channing Laboratory, Brigham and Women s Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
    Cancer Causes Control 16:1099-106. 2005
    ..We prospectively investigated the independent association of hypertension, thiazide use, body mass index, weight change, and smoking with the risk of renal cell carcinoma among men and women using biennial mailed questionnaires...
  75. pmc Mutation-driven drug development in melanoma
    Keith T Flaherty
    Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA
    Curr Opin Oncol 22:178-83. 2010
    ..The purpose of this review is to define those oncogenes for which there are preclinical data supporting clinical trials and to summarize results from clinical investigations...
  76. doi Combined inhibition of MAPK and mTOR signaling inhibits growth, induces cell death, and abrogates invasive growth of melanoma cells
    Konstantinos G Lasithiotakis
    Division of Dermatologic Oncology, Department of Dermatology, University of Tuebingen, Tuebingen, Germany
    J Invest Dermatol 128:2013-23. 2008
    ..Sorafenib combined with rapamycin appears to be a promising strategy for the effective treatment of melanoma and merits clinical investigation...
  77. ncbi Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma
    Mark J Ratain
    University of Chicago, Chicago, IL 60637, USA
    J Clin Oncol 24:2505-12. 2006
    ..This phase II randomized discontinuation trial evaluated the effects of sorafenib (BAY 43-9006), an oral multikinase inhibitor targeting the tumor and vasculature, on tumor growth in patients with metastatic renal cell carcinoma...
  78. ncbi CCR drug updates: sorafenib and sunitinib in renal cell carcinoma
    Mark N Stein
    Department of Medicine, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, The Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA
    Clin Cancer Res 13:3765-70. 2007
  79. pmc Expression of tumor necrosis factor--related apoptosis-inducing ligand receptors 1 and 2 in melanoma
    Mary M McCarthy
    Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Clin Cancer Res 12:3856-63. 2006
    ..We assessed TRAIL-R1 and TRAIL-R2 expression patterns in a large cohort of melanomas and benign nevi...

Research Grants2

  1. Combination Strategies for Angiogenesis Inhibition
    Keith Flaherty; Fiscal Year: 2007
    ..He is a recognized leader in the field of investigational therapies, has a record of mentoring successful clinical researchers, and is committed to Dr. Flaherty's training. ..