Keith T. Flaherty
A5023174631- Melanoma and MAPK Pathways
- Cancer Immunotherapy and Biomarkers
- Cutaneous Melanoma Detection and Management
- CAR-T cell therapy research
- Colorectal Cancer Treatments and Studies
- Computational Drug Discovery Methods
- Cancer Genomics and Diagnostics
- HER2/EGFR in Cancer Research
- Immunotherapy and Immune Responses
- Protein Degradation and Inhibitors
- Cancer Mechanisms and Therapy
- Lung Cancer Treatments and Mutations
- Renal cell carcinoma treatment
- Synthesis and biological activity
- Click Chemistry and Applications
- Synthesis of Tetrazole Derivatives
- Advanced Breast Cancer Therapies
- PI3K/AKT/mTOR signaling in cancer
- Fibroblast Growth Factor Research
- Cancer Research and Treatments
- Renal and related cancers
- Cytokine Signaling Pathways and Interactions
- Cancer, Hypoxia, and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Estrogen and related hormone effects
Massachusetts General Hospital
2016-2025
Harvard University
2016-2025
Center for Cancer Research
2018-2025
Dana-Farber Cancer Institute
2014-2023
The University of Texas MD Anderson Cancer Center
2006-2023
University of Pennsylvania
2008-2023
Palmetto Hematology Oncology
2009-2023
Boston University
2013-2022
Target (United States)
2013-2021
Puma Biotechnology (United States)
2021
Phase 1 and 2 clinical trials of the BRAF kinase inhibitor vemurafenib (PLX4032) have shown response rates more than 50% in patients with metastatic melanoma V600E mutation.
To revise the staging system for cutaneous melanoma on basis of data from an expanded American Joint Committee Cancer (AJCC) Melanoma Staging Database.The recommendations were made a multivariate analysis 30,946 patients with stages I, II, and III 7,972 stage IV to clarify TNM classifications grouping criteria.Findings new definitions include following: (1) in localized melanoma, tumor thickness, mitotic rate (histologically defined as mitoses/mm(2)), ulceration most dominant prognostic...
To explore the distinct genotypic and phenotypic states of melanoma tumors, we applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, endothelial cells. Malignant within same tumor displayed transcriptional heterogeneity associated with cell cycle, spatial context, a drug-resistance program. In particular, all tumors harbored malignant two states, such that characterized by high levels MITF transcription factor also...
The identification of somatic mutations in the gene encoding serine-threonine protein kinase B-RAF (BRAF) majority melanomas offers an opportunity to test oncogene-targeted therapy for this disease.We conducted a multicenter, phase 1, dose-escalation trial PLX4032 (also known as RG7204), orally available inhibitor mutated BRAF, followed by extension involving maximum dose that could be administered without adverse effects (the recommended 2 dose). Patients received twice daily until they had...
Resistance to therapy with BRAF kinase inhibitors is associated reactivation of the mitogen-activated protein (MAPK) pathway. To address this problem, we conducted a phase 1 and 2 trial combined treatment dabrafenib, selective inhibitor, trametinib, MAPK (MEK) inhibitor.
The BRAF inhibitors vemurafenib and dabrafenib have shown efficacy as monotherapies in patients with previously untreated metastatic melanoma V600E or V600K mutations. Combining the MEK inhibitor trametinib, compared alone, enhanced antitumor activity this population of patients.In open-label, phase 3 trial, we randomly assigned 704 a V600 mutation to receive either combination (150 mg twice daily) trametinib (2 once (960 orally first-line therapy. primary end point was overall survival.At...
Approximately 50% of melanomas harbor activating (V600) mutations in the serine–threonine protein kinase B-RAF (BRAF). The oral BRAF inhibitor vemurafenib (PLX4032) frequently produced tumor regressions patients with V600–mutant metastatic melanoma a phase 1 trial and improved overall survival 3 trial.
Activating mutations in serine–threonine protein kinase B-RAF (BRAF) are found 50% of patients with advanced melanoma. Selective BRAF-inhibitor therapy improves survival, as compared chemotherapy, but responses often short-lived. In previous trials, MEK inhibition appeared to be promising this population.
Answer questions and earn CME/CNE To update the melanoma staging system of American Joint Committee on Cancer (AJCC) a large database was assembled comprising >46,000 patients from 10 centers worldwide with stages I, II, III diagnosed since 1998. Based analyses this new database, existing seventh edition AJCC stage IV contemporary clinical trial data, Melanoma Expert Panel introduced several important changes to Tumor, Nodes, Metastasis (TNM) classification grouping criteria. Key in eighth...
Combined BRAF and MEK inhibition, as compared with inhibition alone, delays the emergence of resistance reduces toxic effects in patients who have melanoma V600E or V600K mutations.
In model systems, bacteria present in human pancreatic tumors confer resistance to the anticancer drug gemcitabine.
Background Activating mutations in serine–threonine protein kinase B-RAF (BRAF) are found 50% of patients with advanced melanoma. Selective BRAF-inhibitor therapy improves survival, as compared chemotherapy, but responses often short-lived. In previous trials, MEK inhibition appeared to be promising this population. Methods In phase 3 open-label trial, we randomly assigned 322 who had metastatic melanoma a V600E or V600K BRAF mutation receive either trametinib, an oral selective...
Patients who have unresectable or metastatic melanoma with a BRAF V600E V600K mutation prolonged progression-free survival and overall when receiving treatment inhibitors plus MEK inhibitors. However, long-term clinical outcomes in these patients remain undefined. To determine 5-year rates characteristics of the durable benefit, we sought to review data from randomized trials combination therapy
This phase II randomized discontinuation trial evaluated the effects of sorafenib (BAY 43-9006), an oral multikinase inhibitor targeting tumor and vasculature, on growth in patients with metastatic renal cell carcinoma.Patients initially received 400 mg twice daily during initial run-in period. After 12 weeks, changes bidimensional measurements that were less than 25% from baseline randomly assigned to or placebo for additional weeks; > = shrinkage continued open-label sorafenib;...
Cutaneous squamous-cell carcinomas and keratoacanthomas are common findings in patients treated with BRAF inhibitors.