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

---

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.

More on [ Trastuzumab ]

Trastuzumab - Twitter Search

paclitaxel & trastuzumab and/or lapatinib in treating ppl w/ stage ii or stage iii breast cancer tht can b removed by http://bit.ly/7ABKZz
latrials (LA trials) Thu, 17 Dec 2009 04:35:28 -0000
paclitaxel & trastuzumab and/or lapatinib in treating ppl w/ stage ii or stage iii breast cancer tht can b removed by http://bit.ly/7ABKZz
Adjuvant trastuzumab induces ventricular remodeling despite aerobic exercise training. http://bit.ly/4qoQRn
_familymedicine (John Johnston) Thu, 17 Dec 2009 03:08:53 -0000
Adjuvant trastuzumab induces ventricular remodeling despite aerobic exercise training. http://bit.ly/4qoQRn
Chemotherapy: CANCER AND IMPORTANT MEDICAL NEWS: USE TRASTUZUMAB WITH CHEMOTHERAPY http://bit.ly/6hyiYO
lefernald (Fernald Leeanne) Wed, 16 Dec 2009 22:12:16 -0000
Chemotherapy: CANCER AND IMPORTANT MEDICAL NEWS: USE TRASTUZUMAB WITH CHEMOTHERAPY http://bit.ly/6hyiYO
#Oncology Concurrent Trastuzumab Is Best in HER2 Breast Cancer http://bit.ly/6prnbd
MedscapeOnc (Medscape Oncology) Wed, 16 Dec 2009 15:19:11 -0000
#Oncology Concurrent Trastuzumab Is Best in HER2 Breast Cancer http://bit.ly/6prnbd
Lapatinib plus trastuzumab significantly better than lapatinib alone in extending HER2+ bc patients lives. http://tinyurl.com/yfbu7f3
breastnews (Steven Sickles) Wed, 16 Dec 2009 13:37:42 -0000
Lapatinib plus trastuzumab significantly better than lapatinib alone in extending HER2+ bc patients lives. http://tinyurl.com/yfbu7f3
Novel Form of Trastuzumab Works in Refractory Metastatic Breast CA - http://bit.ly/7ixPTw
jdarsee (JR Hughes-Darsee MD) Wed, 16 Dec 2009 11:26:57 -0000
Novel Form of Trastuzumab Works in Refractory Metastatic Breast CA - http://bit.ly/7ixPTw

Subscribe to Trastuzumab RSS feed