PIK3CAH1047R-induced paradoxical ERK activation results in resistance to BRAFV600E specific inhibitors in BRAFV600E PIK3CAH1047R double mutant thyroid tumors

PIK3CAH1047R-induced paradoxical ERK activation results in resistance to BRAFV600E specific inhibitors in BRAFV600E PIK3CAH1047R double mutant thyroid tumors

Thyroid carcinomas are the most prevalent endocrine cancers. The BRAFV600E mutation is found in 40% of the papillary type and 25% of the anaplastic type. BRAFV600E inhibitors have shown great success in melanoma but, they have been, to date, less successful in thyroid cancer. About 50% of anaplastic thyroid carcinomas present mutations/amplification of the phosphatidylinositol 3' kinase. Here w...

PIK3CA-induced paradoxical ERK activation results in resistance to BRAF specific inhibitors in BRAF PIK3CA double mutant thyroid tumors

Acquired resistance to BRAF inhibition in BRAFV600E mutant gliomas

Activating mutation of BRAF is a common finding in pediatric gliomas. As many as 14% of high grade and up to 66% of certain subtypes of low grade pediatric glioma have the BRAFV600E mutation. Small molecule inhibitors that selectively target BRAFV600E are FDA approved for melanoma and have shown significant efficacy in treating BRAFV600E glioma in pre-clinical trials. Despite showing initial an...

Differential AKT dependency displayed by mouse models of BRAFV600E-initiated melanoma.

Malignant melanoma is frequently driven by mutational activation of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) accompanied by silencing of the phosphatase and tensin homology (PTEN) tumor suppressor. Despite the implied importance of PI3K signaling in PTENNull melanomas, mutational activation of the gene encoding the catalytic subunit of PI3Kα (PIK3CA), is rarely detected. Since PTEN...

Unfavorable efficacy to 131I ablation in BRAFV600E mutant papillary thyroid carcinoma with positive TgAb

The BRAFV600E mutation has shown a close relationship of aggressiveness in papillary thyroid carcinoma (PTC), while it remains unclear about its influence on the therapeutic response. As a common clinicopathologic risk factor, thyroglobulin antibody (TgAb) may have a correlation of prognosis in PTC. The objective was to investigate the relationship between BRAFV600E mutation and TgAb, and their...