Prominent publications by Paul B Chapman

KOL Index score: 20807

Tumors with mutant BRAF and some with mutant RAS are dependent upon ERK signaling for proliferation, and their growth is suppressed by MAPK/ERK kinase (MEK) inhibitors. In contrast, tumor cells with human EGF receptor (HER) kinase activation proliferate in a MEK-independent manner. These findings have led to the development of RAF and MEK inhibitors as anticancer agents. Like MEK inhibitors, the RAF inhibitor PLX4032 inhibits the proliferation of BRAF(V600E) tumor cells but not that of ...

Also Ranks for: Raf Inhibitor |  erk signaling |  tumor cells |  cell proliferation |  kinases mutation
KOL Index score: 19815

BACKGROUND: Obesity has been linked to increased mortality in several cancer types; however, the relation between obesity and survival outcomes in metastatic melanoma is unknown. The aim of this study was to examine the association between body-mass index (BMI) and progression-free survival or overall survival in patients with metastatic melanoma who received targeted therapy, immunotherapy, or chemotherapy.

METHODS: This retrospective study analysed independent cohorts of patients with ...

Also Ranks for: Metastatic Melanoma |  patients bmi |  obesity survival |  antineoplastic agents |  targeted therapy immunotherapy
KOL Index score: 16895

BACKGROUND: In the BRIM-3 trial, vemurafenib was associated with risk reduction versus dacarbazine of both death and progression in patients with advanced BRAF(V600) mutation-positive melanoma. We present an extended follow-up analysis of the total population and in the BRAF(V600E) and BRAF(V600K) mutation subgroups.

METHODS: Patients older than 18 years, with treatment-naive metastatic melanoma and whose tumour tissue was positive for BRAF(V600) mutations were eligible. Patients also ...

Also Ranks for: Vemurafenib Dacarbazine |  braf v600 |  positive melanoma |  months 95 |  median progressionfree survival
KOL Index score: 16738

BACKGROUND: Brain metastases are common in patients with metastatic melanoma and median overall survival from their diagnosis is typically 17-22 weeks. We assessed dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain.

METHODS: We undertook a multicentre, open-label, phase 2 trial in 24 centres in six countries. We enrolled patients with histologically confirmed Val600Glu or Val600Lys BRAF-mutant melanoma and at least one asymptomatic brain ...

Also Ranks for: Patients Cohort |  mutant melanoma |  2 trial |  intracranial response |  brain metastases
KOL Index score: 15401

Melanoma is a disease characterized by lesions that activate ERK. Although 70% of cutaneous melanomas harbor activating mutations in the BRAF and NRAS genes, the alterations that drive tumor progression in the remaining 30% are largely undefined. Vemurafenib, a selective inhibitor of RAF kinases, has clinical utility restricted to BRAF-mutant tumors. MEK inhibitors, which have shown clinical activity in NRAS-mutant melanoma, may be effective in other ERK pathway-dependent settings. Here, ...

Also Ranks for: Cutaneous Melanoma |  ras activation |  loss nf1 |  skin neoplasms |  mek dependence
KOL Index score: 15310

BACKGROUND: Dabrafenib, an inhibitor of mutated BRAF, has clinical activity with a manageable safety profile in studies of phase 1 and 2 in patients with BRAF(V600)-mutated metastatic melanoma. We studied the efficacy of dabrafenib in patients with BRAF(V600E)-mutated metastatic melanoma.

METHODS: We enrolled patients in this open-label phase 3 trial between Dec 23, 2010, and Sept 1, 2011. This report is based on a data cutoff date of Dec 19, 2011. Patients aged 18 years or older with ...

Also Ranks for: Dabrafenib Patients |  phase 3 |  randomised controlled trial |  antineoplastic agents |  mutated metastatic
KOL Index score: 14300

Importance: Nivolumab plus ipilimumab (nivo + ipi) is a standard treatment of advanced melanoma. Two randomized trials describe high objective response rates by Response Evaluation Criteria in Solid Tumors. The trials assessed toxic effects using the Common Terminology Criteria for Adverse Events (CTCAE), which may underestimate incidence of clinically significant immune-related adverse events (AEs).

Objective: To describe detailed toxic effects and time to treatment failure of patients ...

Also Ranks for: Treatment Failure |  toxic effects |  patients melanoma |  4 doses |  nivolumab ipilimumab
KOL Index score: 14070

IMPORTANCE: Uveal melanoma is characterized by mutations in GNAQ and GNA11, resulting in mitogen-activated protein kinase pathway activation.

OBJECTIVE: To assess the efficacy of selumetinib, a selective, non-adenosine triphosphate competitive inhibitor of MEK1 and MEK2, in uveal melanoma.

DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label, phase 2 clinical trial comparing selumetinib vs chemotherapy conducted from August 2010 through December 2013 among 120 patients with ...

Also Ranks for: Patients Chemotherapy |  antineoplastic agents |  clinical trial |  uveal melanoma |  hazard ratio
KOL Index score: 14064

Drug resistance presents a challenge to the treatment of cancer patients. Many studies have focused on cell-autonomous mechanisms of drug resistance. By contrast, we proposed that the tumour micro-environment confers innate resistance to therapy. Here we developed a co-culture system to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anticancer drugs. We found that stroma-mediated resistance is common, ...

Also Ranks for: Innate Resistance |  brafmutant melanoma |  tumor microenvironment |  stromal cell |  targeted agents
KOL Index score: 13588

PURPOSE: Ipilimumab is a standard treatment for metastatic melanoma, but immune-related adverse events (irAEs) are common and can be severe. We reviewed our large, contemporary experience with ipilimumab treatment outside of clinical trials to determine the frequency of use of systemic corticosteroid or anti-tumor necrosis factor α (anti-TNFα) therapy and the effect of these therapies on overall survival (OS) and time to treatment failure (TTF).


Also Ranks for: Treatment Failure |  patients iraes |  systemic immunosuppression |  ttf irae |  antibodies young adult
KOL Index score: 13112

Tumor cells transduced with cytokine genes provide a model to study host-effector mechanisms involved in tumor rejection. Local IL-2 production within a tumor site mimics a specific helper-T-cell response, bypassing an immunization phase. Growth of mouse B16F10 melanomas transduced with interleukin-2 (IL-2) in syngeneic hosts were significantly delayed. IL-2-producing B16F10 cells were super-transduced with interferon-gamma to up-regulate expression of major-histocompatibility-complex ...

Also Ranks for: Tumor Rejection |  killer cells |  mouse melanoma |  local secretion |  inbred balb mice
KOL Index score: 12243

BACKGROUND: 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.

METHODS: We conducted a multicenter, phase 1, dose-escalation trial of PLX4032 (also known as RG7204), an orally available inhibitor of mutated BRAF, followed by an extension phase involving the maximum dose that could be administered without adverse effects (the ...

Also Ranks for: Metastatic Melanoma |  activated braf |  2 dose patients |  complete response |  recommended phase
KOL Index score: 11944

PURPOSE: To investigate the clinical and morphologic characteristics of serous retinal disturbances in patients taking mitogen-activated protein kinase kinase (MEK) inhibitors.

PARTICIPANTS: A total of 313 fluid foci in 50 eyes of 25 patients receiving MEK inhibitors for treatment of their metastatic cancer, who had evidence of serous retinal detachments confirmed by optical coherence tomography (OCT).

DESIGN: Single-center, retrospective cohort study.

METHODS: Clinical examination and ...

Also Ranks for: Mek Inhibitor |  central serous chorioretinopathy |  fluid foci |  protein kinase |  morphologic characteristics
KOL Index score: 11888

Activated RAS promotes dimerization of members of the RAF kinase family. ATP-competitive RAF inhibitors activate ERK signalling by transactivating RAF dimers. In melanomas with mutant BRAF(V600E), levels of RAS activation are low and these drugs bind to BRAF(V600E) monomers and inhibit their activity. This tumour-specific inhibition of ERK signalling results in a broad therapeutic index and RAF inhibitors have remarkable clinical activity in patients with melanomas that harbour mutant ...

Also Ranks for: Raf Inhibitor |  tumor drug resistance |  ras activation |  patients melanomas |  erk signalling
KOL Index score: 11818

CONTEXT: Some melanomas arising from acral, mucosal, and chronically sun-damaged sites harbor activating mutations and amplification of the type III transmembrane receptor tyrosine kinase KIT. We explored the effects of KIT inhibition using imatinib mesylate in this molecular subset of disease.

OBJECTIVE: To assess clinical effects of imatinib mesylate in patients with melanoma harboring KIT alterations.

DESIGN, SETTING, AND PATIENTS: A single-group, open-label, phase 2 trial at 1 ...

Also Ranks for: Metastatic Melanoma |  therapeutic target |  kit alterations |  imatinib patients |  acral mucosal

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Paul B Chapman:Expert Impact

Concepts for whichPaul B Chapmanhas direct influence:Metastatic melanoma,  Melanoma patients,  Advanced melanoma,  Gd3 ganglioside,  Patients metastatic melanoma,  Patients melanoma,  Uveal melanoma.

Paul B Chapman:KOL impact

Concepts related to the work of other authors for whichfor which Paul B Chapman has influence:Metastatic melanoma,  Extracellular vesicles,  Cancer cells,  Brain metastases,  Immune checkpoint inhibitors,  Tumor microenvironment,  Antineoplastic agents.



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Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA | Weill Cornell Medical College, New York, NY. | Department of Medicine, Weill Cornell Medicine, New York, New York, USA | Memorial Sloan Kettering Cancer Center