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10-02-2004, 02:44 PM
IGF-IR signaling appears to play role in trastuzumab resistance
Last Updated: December 18, 2001
Last Updated: 2001-12-18 16:00:42 EST (Reuters Health) NEW YORK (Reuters Health) - Signaling of the insulin-like growth factor-I receptor (IGF-IR) seems to be involved in the trastuzumab resistance that often occurs during breast cancer treatment, according to a report published in the December 19th issue of the Journal of the National Cancer Institute.
Trastuzumab, produced by San Francisco-based drug company Genentech under the name Herceptin, is used to treat ErbB2-overexpressing breast cancers. However, most cancers become resistant to the drug within 12 months of therapy. The reason for this resistance has been unclear.
Dr. Michael Pollak, from Jewish General Hospital in Montreal, and colleagues used two human breast cancer models to assess the effects of trastuzumab and IGF-I on breast cancer cell growth.
The researchers found that trastuzumab was only effective in inhibiting growth when IGF-IR signaling was minimized. In cells that expressed IGF-IR, trastuzumab's efficacy was dependent on the IGF-I level in the growth media. In contrast, in cells with limited IGF-IR expression, trastuzumab's effects were independent of the IGF-I level present.
Genetically altering cells to express IGF-IR reduced trastuzumab's efficacy when IGF-I was present in the growth media. However, addition of IGF-binding protein-3 decreased IGF-IR signaling and restored trastuzumab's ability to reduce cell proliferation.
The current findings indicate that IGF-IR signaling promotes breast cancer cell resistance to trastuzumab, the authors state. "Strategies that target IGF-IR signaling may prevent or delay development of resistance to trastuzumab."
In a related editorial, Dr. Joan Albanell and Dr. Jose Baselga, from Vall d'Hebron University Hospital in Barcelona, Spain, comment that "if an association between IGF-IR activation and resistance to trastuzumab were established in the clinic, it would be a strong signal to combine anti-IGF-IR and anti-HER2 therapies in patients with breast cancer."
J Natl Cancer Inst 2001;93:1830-1832,1852-1857.
Last Updated: December 18, 2001
Last Updated: 2001-12-18 16:00:42 EST (Reuters Health) NEW YORK (Reuters Health) - Signaling of the insulin-like growth factor-I receptor (IGF-IR) seems to be involved in the trastuzumab resistance that often occurs during breast cancer treatment, according to a report published in the December 19th issue of the Journal of the National Cancer Institute.
Trastuzumab, produced by San Francisco-based drug company Genentech under the name Herceptin, is used to treat ErbB2-overexpressing breast cancers. However, most cancers become resistant to the drug within 12 months of therapy. The reason for this resistance has been unclear.
Dr. Michael Pollak, from Jewish General Hospital in Montreal, and colleagues used two human breast cancer models to assess the effects of trastuzumab and IGF-I on breast cancer cell growth.
The researchers found that trastuzumab was only effective in inhibiting growth when IGF-IR signaling was minimized. In cells that expressed IGF-IR, trastuzumab's efficacy was dependent on the IGF-I level in the growth media. In contrast, in cells with limited IGF-IR expression, trastuzumab's effects were independent of the IGF-I level present.
Genetically altering cells to express IGF-IR reduced trastuzumab's efficacy when IGF-I was present in the growth media. However, addition of IGF-binding protein-3 decreased IGF-IR signaling and restored trastuzumab's ability to reduce cell proliferation.
The current findings indicate that IGF-IR signaling promotes breast cancer cell resistance to trastuzumab, the authors state. "Strategies that target IGF-IR signaling may prevent or delay development of resistance to trastuzumab."
In a related editorial, Dr. Joan Albanell and Dr. Jose Baselga, from Vall d'Hebron University Hospital in Barcelona, Spain, comment that "if an association between IGF-IR activation and resistance to trastuzumab were established in the clinic, it would be a strong signal to combine anti-IGF-IR and anti-HER2 therapies in patients with breast cancer."
J Natl Cancer Inst 2001;93:1830-1832,1852-1857.