Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fulvestrant, the first drug of the pure estrogen antagonists to be approved for clinical use, is a new therapeutic option for metastatic breast cancer. Fulvestrant offers a unique metastatic breast cancer treatment option because its mechanism of action is the destruction, rather than the blockade, of estrogen receptors. No known agonistic activity exists, limiting potential side effects and receptor exhaustion. The side effect profile of fulvestrant is related to its antiestrogen effect and includes gastrointestinal disturbance, urinary tract infection, and vaginitis. Suggestions for managing the side effects of fulvestrant are described, and a case study is provided as an illustrative aid in understanding the role of this new hormonal agent.
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PMID:Hormonal therapy for breast cancer: focus on fulvestrant. 1279 37

Immune checkpoint blockade (ICB) is efficacious in many diverse cancer types, but not all patients respond. It is important to understand the mechanisms driving resistance to these treatments and to identify predictive biomarkers of response to provide best treatment options for all patients. Here we introduce a resection and response-assessment approach for studying the tumor microenvironment before or shortly after treatment initiation to identify predictive biomarkers differentiating responders from nonresponders. Our approach builds on a bilateral tumor implantation technique in a murine metastatic breast cancer model (E0771) coupled with anti-PD-1 therapy. Using our model, we show that tumors from mice responding to ICB therapy had significantly higher CD8+ T cells and fewer Gr1+CD11b+ myeloid-derived suppressor cells (MDSCs) at early time points following therapy initiation. RNA sequencing on the intratumoral CD8+ T cells identified the presence of T cell exhaustion pathways in nonresponding tumors and T cell activation in responding tumors. Strikingly, we showed that our derived response and resistance signatures significantly segregate patients by survival and associate with patient response to ICB. Furthermore, we identified decreased expression of CXCR3 in nonresponding mice and showed that tumors grown in Cxcr3 -/- mice had an elevated resistance rate to anti-PD-1 treatment. Our findings suggest that the resection and response tumor model can be used to identify response and resistance biomarkers to ICB therapy and guide the use of combination therapy to further boost the antitumor efficacy of ICB.
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PMID:A bilateral tumor model identifies transcriptional programs associated with patient response to immune checkpoint blockade. 3290 39