Inherited pathogenic variants (PVs) in the CDKN2A tumor suppressor gene are among the strongest risk factors for cutaneous melanoma. Dysregulation of the p16/RB1 pathway may intrinsically limit the activity of MAPK-directed therapy due to the interplay between the two pathways. In our study, we assessed, for the first time, whether patients with germline CDKN2A PVs achieve suboptimal results with BRAF inhibitors (BRAFi)+/-MEK inhibitors (MEKi). We compared the response rate of nineteen CDKN2A PVs carriers who received first-line treatment with BRAFi+/-MEKi with an expected rate derived from phase III trials and "real-world" studies. We observed partial response in 16/19 patients (84%), and no complete responses. The overall response rate was higher than that expected from phase III trials (66%), although not statistically significant (-value = 0.143; 95% CI = 0.60-0.97); the difference was statistically significant (-value = 0.019; 95% CI = 0.62-0.97) in the comparison with real-world studies (57%). The clinical activity of BRAFi+/-MEKi in patients with germline CDKN2A PV was not inferior to that of clinical trials and real-world studies, which is of primary importance for clinical management and genetic counseling of this subgroup of patients.
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http://dx.doi.org/10.3390/cancers13102440 | DOI Listing |
Curr Protoc
January 2025
Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Mesothelioma is a lethal cancer of the serosal lining of the body cavities. Risk factors include environmental and genetic factors. Asbestos exposure is considered the principal environmental risk factor, but other carcinogenic mineral fibers, such as erionite, also have a causal role.
View Article and Find Full Text PDFJCO Glob Oncol
January 2025
Servicio de Oncología, Centro Universitario Contra el Cáncer (CUCC), Hospital Universitario "Dr. José Eleuterio González," Universidad Autónoma de Nuevo León, Monterrey, México.
Purpose: Hereditary cancer syndromes (HCS) explain 5%-10% of all cancer cases. Patients with more than one germline pathogenic variant (GPV) result in a clinical syndrome known as multilocus inherited neoplasia allele syndrome (MINAS). In recent years, an increasing number of MINAS cases have been reported.
View Article and Find Full Text PDFMutat Res
December 2024
School of Health Sciences and Technology, UPES, Dehradun, Uttarakhand 248007, India. Electronic address:
Gallbladder cancer (GBC) is an aggressive malignancy with a poor prognosis, often diagnosed at advanced stages due to subtle early symptoms. Recent studies have provided a comprehensive view of GBC's genetic and mutational landscape, uncovering crucial pathways involved in its pathogenesis. Environmental exposures, particularly to heavy metals, have been linked to elevated GBC risk.
View Article and Find Full Text PDFTheranostics
December 2024
Central Laboratory, The First Affiliated Hospital of Hebei North University, 075000, Zhangjiakou, Hebei, China.
Melanoma, the deadliest form of skin cancer characterized by high therapy resistance, has undergone extensive investigation through the utilization of BRAF-driven melanoma animal models. However, there exists a paucity of animal models for the rare hereditary melanoma resulting from germline mutations. Here, employing CRISPR/Cas9 technology, we generated on a knockout background to model human germline mutation-induced hereditary melanoma.
View Article and Find Full Text PDFInt J Dermatol
December 2024
Dermatology Department, Hospital Regional Universitario de Málaga, Malaga, Spain.
The pathogenesis of melanoma is influenced by a complex combination of environmental factors and individual genetic susceptibility. Familial melanoma refers to cases where there are two first-degree relatives with a melanoma diagnosis. Less strict definitions include second-degree relatives or even three or more of any degree from the same family, although this is not clearly defined in the literature.
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