FDA Greenlights New Breast Cancer Therapy, Amidst Data Scrutiny
The FDA approved Veppanu for advanced breast cancer patients with ESR1 mutations who failed prior hormone therapy. Learn what this means for treatment.
#BreastCancer, #Veppanu, #FDA, #CancerTreatment, #ESR1
https://newsletter.tf/fda-approves-veppanu-breast-cancer-esr1-mutation/
The FDA has approved Veppanu, a new breast cancer drug. This is the first PROTAC protein degrader approved for patients with specific mutations.
#BreastCancer, #Veppanu, #FDA, #CancerTreatment, #ESR1
https://newsletter.tf/fda-approves-veppanu-breast-cancer-esr1-mutation/
SciTech Chronicles. . . . . . . . .Mar 17th, 2025
#dementia #nitrate #Porphyromonas #Neisseria #Lookup #Registration #IETF #gTLD
#MIMO #FPA #MRA #SQP #wildfires #mesh #Kinéis #Silvanet #cortical #amygdala #neurobiology #ESR1
From the final exam for "Biomarkers: fact & fiction".
This protein is elevated in invasive ductal carcinoma, compared to other cancers. Discuss research on using ESR1:p & its sequence features to clinically classify breast cancer tumours and its use in selecting treatment option.
#ESR1:p (estrogen receptor 1): Human Protein Atlas mRNA cancer type distribution and GPMDB cancer type tabbulation. #proteomics #winny
Moving from the simplistic definition of #ESR1 and #PIK3CA mutated metastatic #BreastCancer to a more granular resolution of single codon variants thanks to #ctDNA and #LiquidBiopsy for a more precise biological and clinical profiling of #MBC
https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-023-01718-0
Background although being central for the biology and druggability of hormone-receptor positive, HER2 negative metastatic breast cancer (MBC), ESR1 and PIK3CA mutations are simplistically dichotomized as mutated or wild type in current clinical practice. Methods The study analyzed a multi-institutional cohort comprising 703 patients with luminal-like MBC characterized for circulating tumor DNA through next generation sequencing (NGS). Pathway classification was defined based on previous work (i.e., RTK, RAS, RAF, MEK, NRF2, ER, WNT, MYC, P53, cell cycle, notch, PI3K). Single nucleotide variations (SNVs) were annotated for their oncogenicity through OncoKB. Only pathogenic variants were included in the models. Associations among clinical characteristics, pathway classification, and ESR1/PIK3CA codon variants were explored. Results The results showed a differential pattern of associations for ESR1 and PIK3CA codon variants in terms of co-occurring pathway alterations patterns of metastatic dissemination, and prognosis. ESR1 537 was associated with SNVs in the ER and RAF pathways, CNVs in the MYC pathway and bone metastases, while ESR1 538 with SNVs in the cell cycle pathway and liver metastases. PIK3CA 1047 and 542 were associated with CNVs in the PI3K pathway and with bone metastases. Conclusions The study demonstrated how ESR1 and PIK3CA codon variants, together with alterations in specific oncogenic pathways, can differentially impact the biology and clinical phenotype of luminal-like MBC. As novel endocrine therapy agents such as selective estrogen receptor degraders (SERDS) and PI3K inhibitors are being developed, these results highlight the pivotal role of ctDNA NGS to describe tumor evolution and optimize clinical decision making.
#CircRNA CircPVT1 promotes ER-positive #breastcancer tumorigenesis and drug resistance by targeting #ESR1 and #MAVS
New data supporting a deeper #ESR1 variant characterization in #BreastCancer. Y537S is resistant to #SERD #SERM due to stable conformation and activity. L536 shows varying sensitivity, greatest resistance: AZD9833 GDC-0810 RAD1901 #PrecisionMedicine #bcsm
Mutations in the estrogen receptor (ESR1) gene are common in ER-positive breast cancer patients who progress on endocrine therapies. Most mutations localise to just three residues at, or near, the C-terminal helix 12 of the hormone binding domain, at leucine-536, tyrosine-537 and aspartate-538. To investigate these mutations, we have used CRISPR-Cas9 mediated genome engineering to generate a comprehensive set of isogenic mutant breast cancer cell lines. Our results confirm that L536R, Y537C, Y537N, Y537S and D538G mutations confer estrogen-independent growth in breast cancer cells. Growth assays show mutation-specific reductions in sensitivities to drugs representing three classes of clinical anti-estrogens. These differential mutation- and drug-selectivity profiles have implications for treatment choices following clinical emergence of ER mutations. Our results further suggest that mutant expression levels may be determinants of the degree of resistance to some anti-estrogens. Differential gene expression analysis demonstrates up-regulation of estrogen-responsive genes, as expected, but also reveals that enrichment for interferon-regulated gene expression is a common feature of all mutations. Finally, a new gene signature developed from the gene expression profiles in ER mutant cells predicts clinical response in breast cancer patients with ER mutations.
NewsletterTF
John Vaccaro (johniac)
Ron Beavis ❌
Lorenzo Gerratana
The EMBO Journal