Oncotarget

Reviews:

The promise of anti-ErbB3 monoclonals as new cancer therapeutics

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Oncotarget. 2012; 3:744-758. https://doi.org/10.18632/oncotarget.550

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Luigi Aurisicchio, Emanuele Marra, Giuseppe Roscilli, Rita Mancini and Gennaro Ciliberto _

Abstract

Luigi Aurisicchio1,2,6, Emanuele Marra1,6, Giuseppe Roscilli1, Rita Mancini3, Gennaro Ciliberto4,5

1 Takis s.r.l., Via di Castel Romano 100, Roma, Italy

2 BIOGEM scarl, via Camporeale, Ariano Irpino (Av), Italy

3 Dipartimento di Medicina Clinica e Molecolare, Facoltà di Medicina e Psicologia, Università degli Studi di Roma "La Sapienza", Roma

4 IRCCS Istituto Nazionale Tumori, Fondazione “G. Pascale”, Napoli, Italy

5 Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Catanzaro”Magna Graecia”, Catanzaro, Italy

6 These authors contributed equally to this work

Correspondence:

Gennaro Ciliberto, email:

Keywords: : cancer, ErbB3, monoclonal antibodies, mechanism of action, clinical trials

Received: July 13, 2012, Accepted: August 07, 2012, Published: August 10, 2012

Abstract

In the last 3-5 years strong evidence has been gathered demonstrating ErbB3 as a key node for the progression of several cancer types. From the mechanistic standpoint the intracellular region of this receptor is rich of tyrosine residues that, upon phosphorylation, become high affinity binding sites for PI3K and other proteins involved in signal transduction. The involvement of ErbB3 occurs at different levels, most likely as a consequence of its promiscuity in the interaction with other RTKs of the same or other families. Several efforts are therefore being put in the development of antibodies that target this receptor either singly or in combination with other synergizing receptors. Some of these compounds have already entered clinical development. Although clinical proof-of-concept has not yet been achieved, this is likely to occur soon and will further accelerate the inclusion of anti-ErbB3 monoclonals in the repertoire of anticancer agents for more effective combination therapy. In this paper we review the wealth of anti-ErbB3 antibodies under development and compare their properties and potential to become marketed drugs.



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