Purpose: Explore the heterogeneity in dynamics of tumour response to vemurafenib, dabrafenib and trametinib using routinely collected clinical trial imaging data.
Methods: Time-series imaging data from the phase III studies of vemurafenib, dabrafenib and trametinib were collected through a data repository. A mathematical model based on basic mechanisms of tumour growth was placed within a statistical modelling framework to analyse the data.
Results: The analysis revealed: (1) existence of homogeneity in drug response and resistance development within a patient; (2) tumour shrinkage rate does not relate to rate of resistance development; (3) vemurafenib and dabrafenib, two BRAF inhibitors, have different variability in tumour shrinkage rates.
Conclusions: Overall these results show how analysis of the dynamics of individual lesions can shed light on the within and between patient differences in tumour shrinkage and resistance rates, which could be used to gain a macroscopic understanding of tumour heterogeneity.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778167 | PMC |
| http://dx.doi.org/10.1007/s00280-017-3486-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
BRAF inhibitor monotherapy in BRAFV600E-mutated pediatric low-grade glioma: a single center's experience.
Front Oncol
January 2025
Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta, GA, United States.
Background: Pediatric low-grade gliomas (pLGGs) have an overall survival of over 90%; however, patients harboring a BRAF alteration may have worse outcomes, particularly when treated with classic chemotherapy. Combined BRAF/MEK inhibition following incomplete resection demonstrated improved outcome in BRAF altered pLGG compared to combined carboplatin/vincristine chemotherapy and is now considered the standard FDA-approved treatment for this group of tumors. The aim herein was to investigate the efficacy and tolerability of single agent BRAF inhibitor treatment in BRAF altered pLGG.
View Article and Find Full Text PDFAnakinra improves retention rate of targeted treatments in Erdheim-Chester disease.
Rheumatology (Oxford)
January 2025
Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy.
Objective: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that exhibits a wide spectrum of clinical manifestations. The recent identification of activating mutations in the MAPK-ERK pathway in patients with ECD has led to the introduction of targeted therapies. The most commonly used targeted therapies are BRAF- and MEK-inhibitors, which are highly effective but also carry significant toxicity.
View Article and Find Full Text PDFNanomedicine mediated thyroid cancer diagnosis and treatment: an approach from generalized to personalized medicine.
Discov Oncol
December 2024
Department of Medical Oncology Laboratory, All India Institute of Medical Sciences, New Delhi, India.
Thyroid cancer (TC) being the common endocrine malignancy is glooming steadily due to its poor prognosis. The treatment strategies of surgery, radiotherapy, and conventional chemotherapy are providing unsatisfactory output. However, combination therapy can negotiate the worse prognosis to the better, where chemoradiotherapy, radiotherapy with surgery, or dual chemotherapeutic drugs are being glorified.
View Article and Find Full Text PDFNeurologic adverse events associated with BRAF and MEK inhibitor therapy in patients with malignant melanoma: a disproportionality analysis using the Food and Drug Administration Adverse Event Reporting System.
Melanoma Res
December 2024
Department of Dermatology, University of Arizona College of Medicine - Tucson, Tucson, Arizona, USA.
BRAF and MEK inhibitor (BRAFi + MEKi) therapy has improved the treatment of solid tumors with BRAF mutation. However, their neurologic adverse events (nAEs) have been largely unexplored. This study aimed to provide clinicians with more updated knowledge on nAEs associated with BRAFi + MEKi therapy in patients with malignant melanoma compared with nonmelanoma cancers.
View Article and Find Full Text PDFThe evolution of BRAF-targeted therapies in melanoma: overcoming hurdles and unleashing novel strategies.
Front Oncol
November 2024
Department of Biochemistry, Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland.
Melanoma, a highly aggressive form of skin cancer, poses a significant global health burden, with 331,647 new cases and 58,645 deaths reported in 2022. The development of melanoma is influenced by various factors, including sunlight exposure and BRAF mutations that activate the MAPK/ERK pathway. The introduction of BRAF and MEK inhibitors has revolutionized the treatment landscape for melanoma patients.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!