Keith T Flaherty

Summary

Affiliation: Massachusetts General Hospital
Country: USA

Publications

  1. ncbi request reprint 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
  2. doi request reprint 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
  3. pmc Next generation therapies change the landscape in melanoma
    Keith T Flaherty
    Massachusetts General Hospital Cancer Center 55 Fruit Street, Boston, MA 02114 USA
    F1000 Med Rep 3:8. 2011
  4. pmc BRAF in Melanoma: Pathogenesis, Diagnosis, Inhibition, and Resistance
    Ryan J Sullivan
    Division of Hematology Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02114, USA
    J Skin Cancer 2011:423239. 2011
  5. ncbi request reprint 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
  6. doi request reprint 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
  7. doi request reprint 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
  8. 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
  9. doi request reprint 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
  10. doi request reprint BRAF inhibitors and melanoma
    Keith T Flaherty
    Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA
    Cancer J 17:505-11. 2011

Detail Information

Publications79

  1. ncbi request reprint 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
  2. doi request reprint 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...
  3. pmc Next generation therapies change the landscape in melanoma
    Keith T Flaherty
    Massachusetts General Hospital Cancer Center 55 Fruit Street, Boston, MA 02114 USA
    F1000 Med Rep 3:8. 2011
    ....
  4. pmc BRAF in Melanoma: Pathogenesis, Diagnosis, Inhibition, and Resistance
    Ryan J Sullivan
    Division of Hematology Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02114, USA
    J Skin Cancer 2011:423239. 2011
    ..Finally, emerging mechanisms of resistance to BRAF inhibitors and ways of overcoming this resistance are discussed...
  5. ncbi request reprint 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...
  6. doi request reprint 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
    ....
  7. doi request reprint 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...
  8. 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...
  9. doi request reprint 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
    ....
  10. doi request reprint 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...
  11. doi request reprint 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...
  12. doi request reprint Building on a foundation of VEGF and mTOR targeted agents in renal cell carcinoma
    Keith T Flaherty
    Massachusetts General Hospital Cancer Center, Harvard Medical School, 55 Fruit Street, Yawkey 9E, Boston, MA 02114, United States
    Biochem Pharmacol 80:638-46. 2010
    ....
  13. ncbi request reprint 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...
  14. ncbi request reprint 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...
  15. doi request reprint 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
    ..Pharmacokinetic analyses were done for sorafenib on days 2 and 19 of cycle 1 and for paclitaxel on day 1 of cycles 1 and 2. Pretreatment tumor samples from 17 melanoma patients were analyzed for BRAF mutations...
  16. 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...
  17. ncbi request reprint 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...
  18. ncbi request reprint 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...
  19. doi request reprint 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
    ....
  20. doi request reprint 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...
  21. ncbi request reprint Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin
    F Stephen Hodi
    F Stephen Hodi, Anita Giobbie Hurder, Philip Friedlander, Jason J Luke, Katherine A Zukotynski, Jeffrey T Yap, Annick D Van den Abbeele, and George D Demetri, Dana Farber Cancer Institute Jonathan A Fletcher, Meijun Zhu, and Adrian Marino Enriquez, Brigham and Women s Hospital Donald Lawrence, Keith T Flaherty, and David E Fisher, Massachusetts General Hospital, Boston, MA Christopher L Corless, Michael C Heinrich, and Carol Beadling, Portland Veterans Administration Medical Center and Oregon Health and Science University, Portland, OR Philip Friedlander, Mount Sinai Medical Center, New York, NY Rene Gonzalez, University of Colorado Cancer Center, Aurora, CO Jeffrey S Weber, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL Thomas F Gajewski, University of Chicago, Chicago, IL Steven J O Day, Beverly Hills Cancer Center, Beverly Hills, Office of Analysis and Epidemiology
    J Clin Oncol 31:3182-90. 2013
    ..Amplifications and mutations in the KIT proto-oncogene in subsets of melanomas provide therapeutic opportunities...
  22. doi request reprint 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...
  23. doi request reprint 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...
  24. doi request reprint 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...
  25. ncbi request reprint 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...
  26. ncbi request reprint 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...
  27. 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
    ....
  28. 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. ..
  29. 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
    ....
  30. ncbi request reprint 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...
  31. 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...
  32. doi request reprint 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
    ....
  33. doi request reprint 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...
  34. 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
    ....
  35. ncbi request reprint 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...
  36. 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
    ....
  37. doi request reprint 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...
  38. 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...
  39. 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...
  40. ncbi request reprint 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...
  41. ncbi request reprint 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...
  42. ncbi request reprint The intersection of immune-directed and molecularly targeted therapy in advanced melanoma: where we have been, are, and will be
    Ryan J Sullivan
    Authors Affiliations Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts and Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
    Clin Cancer Res 19:5283-91. 2013
    ..This overview presents the historical context to this therapeutic revolution, reviews the benefits and limitations of current therapies, and provides a look ahead at where the field is headed...
  43. ncbi request reprint 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...
  44. 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...
  45. ncbi request reprint 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...
  46. ncbi request reprint 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...
  47. pmc Correlation of somatic mutations and clinical outcome in melanoma patients treated with Carboplatin, Paclitaxel, and sorafenib
    Melissa A Wilson
    Authors Affiliations Hematology Oncology, Department of Medicine, University of Pennsylvania Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania Abramson Cancer Center of the University of Pennsylvania, Philadelphia University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania Dana Farber Cancer Institute Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, Massachusetts Department of Pathology, Yale University School of Medicine and Section of Medical Oncology, Yale Cancer Center, New Haven, Connecticut
    Clin Cancer Res 20:3328-37. 2014
    ..We assessed the association of somatic mutations with clinicopathologic features and clinical outcomes in patients with metastatic melanoma treated on E2603, comparing treatment with carboplatin, paclitaxel ± sorafenib (CP vs...
  48. ncbi request reprint Genetic alterations and personalized medicine in melanoma: progress and future prospects
    Klaus G Griewank
    Affiliations of authors Department of Dermatology, University Hospital, University Duisburg Essen, Essen, Germany KGG, DS Royal Prince Alfred Hospital, Camperdown, NSW, Australia RAS University of Sydney, Camperdown, NSW, Australia RAS, JFT Melanoma Institute Australia, North Sydney, NSW, Australia RAS, JFT Center for Melanoma, Massachusetts General Hospital Cancer Center, Boston, MA KTF Department of Pathology, and Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY RM
    J Natl Cancer Inst 106:djt435. 2014
    ..These developments in melanoma serve as a model for the implementation of personalized medicine for patients with all cancers. ..
  49. ncbi request reprint 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...
  50. doi request reprint 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. ..
  51. doi request reprint Meeting report: consensus from the first and second Global Workshops in Melanoma November 19-20, 2008
    Sanjiv S Agarwala
    Oncology and Hematology, St Luke s Cancer Center, Bethlehem, PA, USA
    Pigment Cell Melanoma Res 22:532-43. 2009
    ....
  52. ncbi request reprint 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...
  53. ncbi request reprint 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
    ....
  54. doi request reprint 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...
  55. ncbi request reprint 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...
  56. ncbi request reprint Hyperspectral imaging: a non-invasive method of imaging melanoma lesions in a patient with stage IV melanoma, being treated with a RAF inhibitor
    David T Dicker
    Penn State Hershey Cancer Institute, Hershey, PA, USA
    Cancer Biol Ther 12:326-34. 2011
    ..PARISS may be useful to better establish a noninvasive means of following disease progression, and ultimately establish characteristic spectral signatures to define disease presence in the future...
  57. doi request reprint 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...
  58. doi request reprint 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
    ....
  59. ncbi request reprint 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
    ....
  60. doi request reprint 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...
  61. ncbi request reprint VEGFR-targeted therapy
    Keith T Flaherty
    Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA
    Clin Adv Hematol Oncol 3:371-2. 2005
  62. 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...
  63. ncbi request reprint 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...
  64. ncbi request reprint 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...
  65. ncbi request reprint 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...
  66. ncbi request reprint 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
  67. ncbi request reprint 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...
  68. 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...
  69. ncbi request reprint 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...
  70. doi request reprint 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. doi request reprint 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
    ....
  72. ncbi request reprint 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...
  73. doi request reprint 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...
  74. 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...
  75. ncbi request reprint 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...
  76. 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...
  77. pmc Phase II and biomarker study of the dual MET/VEGFR2 inhibitor foretinib in patients with papillary renal cell carcinoma
    Toni K Choueiri
    Dana Farber Cancer Institute, Boston, MA, USA
    J Clin Oncol 31:181-6. 2013
    ..Activating mutations or amplifications in MET have been described in patients with papillary renal cell carcinoma (PRCC). We aimed to evaluate the efficacy and safety of foretinib in patients with PRCC...
  78. ncbi request reprint 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...
  79. ncbi request reprint 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...