Trastuzumab (Herceptin®) is an anti-cancer therapy that acts on the HER2/neu (erbB2) receptor. Herceptin's principal use is in breast cancer in patients whose tumors overexpress (produce more than the usual amount of) this receptor. Trastuzumab is administered either once a week or once every three weeks intravenously for 30 to 90 minutes.

Mechanism of action

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Amplification of ErbB2 occurs in 30% of early-stage breast cancers (Bange et al 2001). It encodes the transmembrane tyrosine kinase p185-erbB2 glycoprotein. Although the signaling pathways induced by the erbB2 receptor are incompletely characterized, it is thought that activation of the PI3K/Akt pathway is important. This pathway is normally associated with mitogenic signaling involving the MAPK pathway. In cancer growth producing signals from erbB2 are constitutively transmitted, promoting invasion, survival and angiogenesis of cells (Ménard et al 2003). Furthermore overexpression can also confer therapeutic resistance to cancer therapies. Kute et al. (2004) suggest that the prime mechanism that causes increase in proliferation speed is due to induction of p27Kip1, an inhibitor of cdk2 and of cell proliferation, to remain in the cytoplasm instead of translocation in to the nucleus. This is caused by phosphorylation by Akt.

Herceptin is a monoclonal antibody which binds to the extracellular segment of the erbB2 receptor. Cells treated with Herceptin undergo arrest during the G1 phase of the cell cycle and experience a reduction in proliferation. It has been suggested that Herceptin induces some of its effect by downregulation of erbB2 leading to disruption of receptor dimerization and signaling through the downstream PI3K cascade. P27Kip1 is then not phosphorylated and is able to enter the nucleus and inhibit cdk2 activity, causing cell cycle arrest (Kute et al 2004). Also, Herceptin suppresses angiogenesis by induction of antiangiogenic factors and repression of proangiogenic factors. It is thought that a contribution to the unregulated growth observed in cancer could be due to proteolytic cleavage of erbB2 that results in the release of the extracellular domain. Herceptin has been shown to inhibit erbB2 ectodomain cleavage in breast cancer cells (Albenall et al 2003). There may be other undiscovered mechanisms by which Herceptin induces regression in cancer.

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Clinical Trial Name - Celecoxib and Trastuzumab in Treating Women With Metastatic Breast Cancer http://bit.ly/TCNNl
trialscentral (Trials Central) Sun, 08 Nov 2009 17:14:40 -0000
Clinical Trial Name - Celecoxib and Trastuzumab in Treating Women With Metastatic Breast Cancer http://bit.ly/TCNNl
HER2-positive Breast Cancer can be Safely Treated With Trastuzumab and Adjuvant http://tinyurl.com/yhwzdgj
TheGivingForest (The Giving Forest) Sun, 08 Nov 2009 07:25:36 -0000
HER2-positive Breast Cancer can be Safely Treated With Trastuzumab and Adjuvant http://tinyurl.com/yhwzdgj
Immunoselection of breast and ovarian cancer cells with trastuzumab and natural killer cells http://bit.ly/2jlOYs #cancersc
jimtill (Jim Till) Sat, 07 Nov 2009 20:21:08 -0000
Immunoselection of breast and ovarian cancer cells with trastuzumab and natural killer cells http://bit.ly/2jlOYs #cancersc
Radiology publications: Understanding the Mechanisms Behind Trastuzumab Therapy for Human E... http://bit.ly/1HrG5V
Radiology_help (Radiology help) Fri, 06 Nov 2009 21:49:53 -0000
Radiology publications: Understanding the Mechanisms Behind Trastuzumab Therapy for Human E... http://bit.ly/1HrG5V
temozolamida 250mg (R$7.651,00), trastuzumab (R$ 11.940,00), Sunitinibe 50mg (R$ 20.837,90)... o que acontece com quem não tem dinheiro?
faelssantana (Rafael S. Santana) Fri, 06 Nov 2009 10:30:03 -0000
temozolamida 250mg (R$7.651,00), trastuzumab (R$ 11.940,00), Sunitinibe 50mg (R$ 20.837,90)... o que acontece com quem não tem dinheiro?
Study Finds it's Safe to Treat HER2-Positive Breast Cancer Patients with both Trastuzumab http://tinyurl.com/yk83jfz
TheGivingForest (The Giving Forest) Fri, 06 Nov 2009 09:56:44 -0000
Study Finds it's Safe to Treat HER2-Positive Breast Cancer Patients with both Trastuzumab http://tinyurl.com/yk83jfz

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