Herceptin pretreatment enhances Taxol's effect in ErbB2-overexpressing cells.

2003 JAN 9 - (NewsRx.com & NewsRx.net) -- M.D. Anderson Cancer Center researchers point out that "[t]he recombinant humanized anti-ErbB2/HER2 monoclonal antibody Herceptin (Trastuzumab) has been shown to significantly enhance the tumoricidal effects of antitumor drugs such as paclitaxel (Taxol) in patients with ErbB2-overexpressing breast cancers"

S. Lee and colleagues at the Center "investigated the molecular mechanisms by which Herceptin enhances the antitumor effects of Taxol."

They explained that since "activation of p34(Cdc2) is required for Taxol-induced apoptosis and because overexpression of ErbB2 blocks Taxol-induced apoptosis by inhibiting p34(Cdc2) activation, we studied the effect of Herceptin treatment on p34(Cdc2) kinase activation and apoptosis in Taxol-treated human breast carcinoma cell lines MDA-MB-435, SKBr3, MDA-MB-453, and 435.eB, which is an ErbB2 transfectant of MDA-MB-435."

The researchers reported that "Herceptin treatment down-regulated ErbB2, reduced the inhibitory phosphorylation of Cdc2 on Tyr-15, and down-regulated the expression of p21(CiP1), a Cdc2 inhibitor."

"Herceptin plus Taxol treatment led to higher levels of p34(Cdc2) kinase activity and apoptosis in ErbB2-overexpressing breast cancer cells, which is likely attributable to inhibition of Cdc2-Tyr-15 phosphorylation and p21(CiP1) expression," Lee's group wrote.

"Because significant dephosphorylation of Cdc2-Tyr-15 and down-regulation of p21(CiP1) occur at least 24 hours after Herceptin treatment, we investigated whether 24-hour Herceptin pretreatment will render ...