Abstract
Individualization of cancer management requires prognostic markers and therapy-predictive markers. Prognostic markers assess risk of disease progression independent of therapy, whereas therapy-predictive markers identify patients whose disease is sensitive or resistant to treatment. We show that an experimentally derived IFN-related DNA damage resistance signature (IRDS) is associated with resistance to chemotherapy and/or radiation across different cancer cell lines. The IRDS genes STAT1, ISG15, and IFIT1 all mediate experimental resistance. Clinical analyses reveal that IRDS(+) and IRDS(-) states exist among common human cancers. In breast cancer, a seven-gene-pair classifier predicts for efficacy of adjuvant chemotherapy and for local-regional control after radiation. By providing information on treatment sensitivity or resistance, the IRDS improves outcome prediction when combined with standard markers, risk groups, or other genomic classifiers.
| Original language | English |
|---|---|
| Pages (from-to) | 18490-18495 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 105 |
| Issue number | 47 |
| DOIs | |
| State | Published - Nov 25 2008 |
| Externally published | Yes |
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An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer. / Weichselbaum, Ralph R.; Ishwaran, Hemant; Yoon, Taewon; Nuyten, Dimitry S A; Baker, Samuel W.; Khodarev, Nikolai; Su, Andy W.; Shaikh, Arif Y.; Roach, Paul; Kreike, Bas; Roizman, Bernard; Bergh, Jonas; Pawitan, Yudi; Van De Vijver, Marc J.; Minn, Andy J.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 47, 25.11.2008, p. 18490-18495.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer
AU - Weichselbaum, Ralph R.
AU - Ishwaran, Hemant
AU - Yoon, Taewon
AU - Nuyten, Dimitry S A
AU - Baker, Samuel W.
AU - Khodarev, Nikolai
AU - Su, Andy W.
AU - Shaikh, Arif Y.
AU - Roach, Paul
AU - Kreike, Bas
AU - Roizman, Bernard
AU - Bergh, Jonas
AU - Pawitan, Yudi
AU - Van De Vijver, Marc J.
AU - Minn, Andy J.
PY - 2008/11/25
Y1 - 2008/11/25
N2 - Individualization of cancer management requires prognostic markers and therapy-predictive markers. Prognostic markers assess risk of disease progression independent of therapy, whereas therapy-predictive markers identify patients whose disease is sensitive or resistant to treatment. We show that an experimentally derived IFN-related DNA damage resistance signature (IRDS) is associated with resistance to chemotherapy and/or radiation across different cancer cell lines. The IRDS genes STAT1, ISG15, and IFIT1 all mediate experimental resistance. Clinical analyses reveal that IRDS(+) and IRDS(-) states exist among common human cancers. In breast cancer, a seven-gene-pair classifier predicts for efficacy of adjuvant chemotherapy and for local-regional control after radiation. By providing information on treatment sensitivity or resistance, the IRDS improves outcome prediction when combined with standard markers, risk groups, or other genomic classifiers.
AB - Individualization of cancer management requires prognostic markers and therapy-predictive markers. Prognostic markers assess risk of disease progression independent of therapy, whereas therapy-predictive markers identify patients whose disease is sensitive or resistant to treatment. We show that an experimentally derived IFN-related DNA damage resistance signature (IRDS) is associated with resistance to chemotherapy and/or radiation across different cancer cell lines. The IRDS genes STAT1, ISG15, and IFIT1 all mediate experimental resistance. Clinical analyses reveal that IRDS(+) and IRDS(-) states exist among common human cancers. In breast cancer, a seven-gene-pair classifier predicts for efficacy of adjuvant chemotherapy and for local-regional control after radiation. By providing information on treatment sensitivity or resistance, the IRDS improves outcome prediction when combined with standard markers, risk groups, or other genomic classifiers.
UR - http://www.scopus.com/inward/record.url?scp=57449088412&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=57449088412&partnerID=8YFLogxK
U2 - 10.1073/pnas.0809242105
DO - 10.1073/pnas.0809242105
M3 - Article
C2 - 19001271
AN - SCOPUS:57449088412
VL - 105
SP - 18490
EP - 18495
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 47
ER -