Trastuzumab (Herceptin) — a monoclonal antibody that targets the ERBB2 receptor — has achieved great success in treating breast cancer patients, but can this success be improved on? Mark Sliwkowski and colleagues, reporting in the August issue of Cancer Cell, have developed a new antibody that might do just that.

The limitation of trastuzumab is that it is only effective for the women whose cancers overexpress ERBB2; however, the pathway is also activated in other cancers. ERBB2 acts as a coreceptor — it does not bind its own ligand — in the ERBB signalling pathway, so Sliwkowski and colleagues developed an anti-ERBB2 monoclonal antibody, 2C4, that was able to prevent the heregulin-induced binding of ERBB2 and ERBB3. 2C4 was also able to inhibit the activation of mitogen-activated protein kinase and AKT, two of the key downstream targets of the ERBB pathway.

But can 2C4 actually inhibit tumour growth? It was effective in cell lines and breast cancer xenograft models and, importantly, it was able to prevent growth in xenograft tumours that expressed low levels of ERBB2, for which trastuzumab was unsuccessful.

The ERBB pathway has also been implicated in the growth and survival of prostate cancer cells, and in their progression from an androgen-dependent to an androgen-independent state. Like trastuzumab, 2C4 was able to inhibit the growth of androgen-dependent prostate cancer xenografts. However, unlike trastuzumab, 2C4 was also effective against androgen-independent prostate cancer xenografts.

So, the 2C4 antibody shows great promise as a therapeutic agent against two different cancer types — one of which is particularly difficult to treat. A humanized version has already been developed and found equally effective. We await its entry into clinical trials with great interest.