Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0278488 (
metastatic breast cancer
)
7,812
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Urokinase plasminogen activator
(
uPA
) is an extracellular matrix-degrading protease involved in cancer invasion and metastasis, interacting with plasminogen activator inhibitor-1 (PAI-1), which was originally identified as a blood-derived endogenous fast-acting inhibitor of
uPA
. At concentrations found in tumor tissue, however, both PAI-1 and
uPA
promote tumor progression and metastasis. Consistent with the causative role of
uPA
and PAI-1 in cancer dissemination, several retrospective and prospective studies have shown that elevated levels of
uPA
and PAI-1 in breast tumor tissue are statistically independent and potent predictors of poor patient outcome, including adverse outcome in the subset of breast cancer patients with lymph node-negative disease. In addition to being prognostic, high levels of
uPA
and PAI-1 have been shown to predict benefit from adjuvant chemotherapy in patients with early breast cancer. The unique clinical utility of
uPA
/PAI-1 as prognostic biomarkers in lymph node-negative breast cancer has been confirmed in two independent level-of-evidence-1 studies (that is, in a randomized prospective clinical trial in which the biomarker evaluation was the primary purpose of the trial and in a pooled analysis of individual data from retrospective and prospective studies). Thus,
uPA
and PAI-1 are among the best validated prognostic biomarkers currently available for lymph node-negative breast cancer, their main utility being the identification of lymph node-negative patients who have HER-2-negative tumors and who can be safely spared the toxicity and costs of adjuvant chemotherapy. Recently, a phase II clinical trial using the low-molecular-weight
uPA
inhibitor WX-671 reported activity in
metastatic breast cancer
.
...
PMID:uPA and PAI-1 as biomarkers in breast cancer: validated for clinical use in level-of-evidence-1 studies. 2567 49
