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)

The purpose of this study was to compare the diagnostic significance of serum tumor markers in metastatic breast cancer and to evaluate their usefulness in monitoring palliative treatment. One hundred sixty-two breast cancer patients with various disease involvement have been followed-up by serum beta-human chorionic gonadotrophin (beta-HCG), alkaline phosphatase (AP), phosphohexose isomerase (PHI), carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) analysis for 6 to 29 months. In metastatic disease, rates of elevated tumor marker levels ranging between 44% and 91% were found except for beta-HCG (13%). The low rate of positive beta-HCG values did not suggest that routine estimation may be useful. For the other markers, differences in positive rates were seen when site of metastasis, tumor burden, tumor activity, and stage of disease were taken into account. CEA and TPA were shown to be more sensitive indicators for metastatic disease than AP and PHI. TPA was more sensitive but less specific than CEA; both provided almost identical discrimination. In monitoring palliative treatment, a close correlation was found between the clinical course and changes of CEA. AP and PHI frequently became elevated only in very advanced disease, their elevation supported the clinical evidence of progression.
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PMID:Serum tumor markers in metastatic breast cancer and course of disease. 619 67

Breast cancer includes high number of molecular entities targetable by specific agents. In this study, array CGH and PIK3CA/AKT1 mutations were used to drive patients into targeted therapy. A prospective molecular analysis was offered to metastatic breast cancer patients for whom samples were collected prospectively or retrospectively either from frozen or paraffin-embedded tissue. Analyses were performed using array CGH (Agilent platform) and PIK3CA (exon 10 and 21) and AKT1 mutations were explored by standard Sanger sequencing. One hundred and eight patients were included. Good quality CGH was obtained in 79% cases and was better for frozen samples. Genomic alterations were identified in 50% of patients including 11 PIK3CA and 8 AKT1 mutations. Eighteen treatments (17 patients) were administered according to their molecular profile with evidence of activity in nine. Reasons for not providing a genomic-driven treatment included absence of progressive disease (38%), investigator's choice (9%), rapid PD (19%), and no drug access (21%). Array CGH correctly identified Her2 status in 97% cases; failures were related to low % of tumour cells. Our study showed that array CGH is feasible in the context of daily practice and, in combination with PIK3CA/AKT1 mutations, identifies a significant number of actionable molecular alterations that allow driving patients into specific targeted agents.
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PMID:Array CGH and PIK3CA/AKT1 mutations to drive patients to specific targeted agents: a clinical experience in 108 patients with metastatic breast cancer. 2284 Mar 69

Poly (ADP-ribose) polymerase 1 (PARP1) is an enzyme involved in DNA repair under investigation as a chemotherapeutic target. Current randomized phase three trials of PARPi in metastatic breast cancer are limited to patients with documented BRCA1/2 mutations and no biomarker of PARPi beyond BRCA status is available. In an effort to identify novel biomarkers for PARP inhibition, we created a cell line (HCC1187/TALRES) resistant to the PARP1 inhibitor talazoparib. Herein we show by array-CGH that HCC1187/TALRES has a selective loss of the proteasome ubiquitin receptor PSMD4 amplicon resulting in significant down-regulation of PSMD4. Conversely, we find that breast cancer cell lines that have copy number gain or amplification for PSMD4 are significantly more sensitive to talazoparib. Functional studies reveal that knock-down of PSMD4 in amplified breast cancer cells and loss of the PSMD4 amplicon result in knock-down of PARP1 protein. We show that PSMD4 is amplified and overexpressed in breast cancer and its overexpression correlates with poor survival. Knock-down of PSMD4 results in a significant decrease in cell growth. We provide evidence that PSMD4 is a proteasomal amplification target in breast cancer that PSMD4 amplification confers sensitivity to PARP inhibition, and that PSMD4 amplification is lost in the process of acquiring resistance to PARPi. Finally, this study shows not only that PSMD4 copy number correlates with PARPi sensitivity, but also, that it may be a better predictor of sensitivity to PARPi than BRCA1/2 mutation.
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PMID:Proteasome ubiquitin receptor PSMD4 is an amplification target in breast cancer and may predict sensitivity to PARPi. 2831 10