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Ref Type Journal Article
PMID (26843189)
Authors Arena S, Siravegna G, Mussolin B, Kearns JD, Wolf BB, Misale S, Lazzari L, Bertotti A, Trusolino L, Adjei AA, Montagut C, Di Nicolantonio F, Nering R, Bardelli A
Title MM-151 overcomes acquired resistance to cetuximab and panitumumab in colorectal cancers harboring EGFR extracellular domain mutations.
Journal Vol Issue Date Pages Journal Short Title
Science translational medicine 8 324 2016 Feb 03 324ra14 Sci Transl Med
URL
Abstract Text The anti-epidermal growth factor receptor (EGFR) antibodies cetuximab and panitumumab are used to treat RAS wild-type colorectal cancers (CRCs), but their efficacy is limited by the emergence of acquired drug resistance. After EGFR blockade, about 20% of CRCs develop mutations in the EGFR extracellular domain (ECD) that impair antibody binding and are associated with clinical relapse. We hypothesized that EGFR ECD-resistant variants could be targeted by the recently developed oligoclonal antibody MM-151 that binds multiple regions of the EGFR ECD. MM-151 inhibits EGFR signaling and cell growth in preclinical models, including patient-derived cells carrying mutant EGFR. Upon MM-151 treatment, EGFR ECD mutations decline in circulating cell-free tumor DNA (ctDNA) of CRC patients who previously developed resistance to EGFR blockade. These data provide molecular rationale for the clinical use of MM-151 in patients who become resistant to cetuximab or panitumumab as a result of EGFR ECD mutations.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
MM-151 MM-151 0 2
Drug Name Trade Name Synonyms Drug Classes Drug Description
MM-151 EGFR Antibody 56 MM-151 is a combination of three human monoclonal antibodies targeting distinct, non-overlapping epitopes of epidermal growth factor receptor (EGFR), thereby preventing the binding of ligands and inhibiting EGFR-ERK-mediated signaling (PMID: 26843189).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References