Estrogen receptors prediction

Tong, W.D., Perkins, R., Strelitz, R., Collantes, E.R., Keenan, S., Welsh, W.J., Branham, W.S., and Sheehan, D.M., Quantitative structure-activity relationships (QSARs) for estrogen binding to the estrogen receptor predictions across species, Environ. Health Perspect., 105, 1116-1124, 1997a. 

Tong, W. et al.. Quantitative structure-activity relationships (QSARs) for estrogen binding to the estrogen receptor Predictions across species. Environ. Health Perspect., 105,1116, 1997. 

Summary Statistics for Predictive Estrogen Receptor Binding Affinity Models... 

As expected, in vitro transcription assays involving PARP-1, NAD, and PARC illustrate these predicted outcomes (Kim et al, 2004). Even when driven by a transcriptional activator, such as estradiol-bound estrogen receptor, transcription is repressed when PARP-1 is added to chromatin templates. The repression is reversed by NAD+, and the NAD+-dependent effects are reversed by PARC (Kim et al, 2004). This system for transcriptional control shifts new importance onto the enzymes responsible for synthesis of NAD+ in the nucleus, such as nicotinamide mononucleotide adenylyltransferase-1 (Magni et al, 2004). Because NAD+ facilitates the decompaction of chromatin and the derepression of transcription, nuclear NAD+ biosynthetic enzymes may play critical roles as cofactors. 

Oncotype DX (a 21-gene signature) of Genomic Health (Redwood City, CA) is another commercially available gene test for breast cancer. It is currently applied in clinics to predict recurrence of tamoxifen-treated, node-negative, and estrogen-receptor-positive breast cancer (28). 

One of the earliest examples of predicting efficacy has come from studies of breast cancer, where anti-estrogen therapy is clearly effective in patients whose tumors express the estrogen receptor, and ineffective when no such receptors are present. However, even in this well-studied case, current consensus statements recognize an intermediate endocrine response uncertain state, where the exact boundary between endocrine responsive and endocrine response uncertain is undecided, and may well be different in different clinical settings (19). 

Mekenyan, O., Walker, J.D. and Bradbury, S. (2003) Quantitative structure-activity relationship models for prediction of estrogen receptor binding affinity of structurally diverse chemicals. Environ. Toxicol. Chem., 22 (8), 1844-1854. 

Bieche, I., Parfait, B., Doussal, V. L., Olivi, M., Rio, M.-C., Lidereau, R., and Viduad, M. 2001. Identification of CGA as a novel estrogen receptor-responsive gene in breast cancer An outstanding candidate marker to predict the response to endocrine therapy. Cancer Res. 61 1652-1658. 

Esteban, J. M., Ahn, C., Battifora, H., and Felder, B. 1994c. Predictive value of estrogen receptors evaluated by quantitative immunohistochemical analysis in breast cancer. Am. J. Clin. Pathol. 702 S9-S12. 

Harvey, J. M., Cark, G. M., Osborne, C. K., and Allred, D. C. 1991. Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J. Clin. Oncol. 27 1474-1481. 

Bardou, V.-J., Arpino, G., Elledge, R.M., Osborne, C.K., and Clark, G.M. 2003. Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. J. Clin. Oncol. 21, 1973-1979. 

Most steroid-sensitive cancers express specific cell surface receptors. Prednisone-sensitive lymphomas, estrogen-sensitive breast cancers, and prostatic cancers express specific receptors for corticosteroids, estrogens, and androgens, respectively. It is now possible to assay tumor specimens for steroid receptor content and to identify which individual patients are likely to benefit from hormonal therapy. Measurement of the estrogen receptor (ER) and progesterone receptor (PR) proteins in breast cancer tissue is now standard clinical practice. ER or PR positivity predicts response to hormonal therapy, whereas patients whose tumors are ER-negative generally fail to respond to such treatment. 

Hong, H.W., Tong, H., Fang, L., Shi, R., Xie, Q., Wu, J., Perkins, R., Walker, J.D., Branham, W., and Sheehan, D., Prediction of estrogen receptor binding for 58,000 chemicals using an integrated system of a tree-based model with structural alerts, Environ. Health Perspect., 110 29-36, 2002. 

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