| Added by | amaraver |
|---|---|
| Group name | EquipeAM |
| Item Type | Journal Article |
| Title | An oligoclonal antibody durably overcomes resistance of lung cancer to third-generation EGFR inhibitors |
| Creator | Mancini et al. |
| Author | Maicol Mancini |
| Author | Nadège Gaborit |
| Author | Luigi Mazzeo |
| Author | Donatella Romaniello |
| Author | Tomer Meir Salame |
| Author | Moshit Lindzen |
| Author | Georg Mahlknecht |
| Author | Yehoshua Enuka |
| Author | Dominick Ga Burton |
| Author | Lee Roth |
| Author | Ashish Noronha |
| Author | Ilaria Marrocco |
| Author | Dan Adreka |
| Author | Raya Eilam Altstadter |
| Author | Emilie Bousquet |
| Author | Julian Downward |
| Author | Antonio Maraver |
| Author | Valery Krizhanovsky |
| Author | Yosef Yarden |
| Abstract | Epidermal growth factor receptor (EGFR) mutations identify patients with lung cancer who derive benefit from kinase inhibitors. However, most patients eventually develop resistance, primarily due to the T790M second-site mutation. Irreversible inhibitors (e.g., osimertinib/AZD9291) inhibit T790M-EGFR, but several mechanisms, including a third-site mutation, C797S, confer renewed resistance. We previously reported that a triple mixture of monoclonal antibodies, 3×mAbs, simultaneously targeting EGFR, HER2, and HER3, inhibits T790M-expressing tumors. We now report that 3×mAbs, including a triplet containing cetuximab and trastuzumab, inhibits C797S-expressing tumors. Unlike osimertinib, which induces apoptosis, 3×mAbs promotes degradation of the three receptors and induces cellular senescence. Consistent with distinct mechanisms, treatments combining 3×mAbs plus sub-inhibitory doses of osimertinib synergistically and persistently eliminated tumors. Thus, oligoclonal antibodies, either alone or in combination with kinase inhibitors, might preempt repeated cycles of treatment and rapid emergence of resistance. |
| Publication | EMBO molecular medicine |
| Volume | 10 |
| Issue | 2 |
| Pages | 294-308 |
| Date | 02 2018 |
| Journal Abbr | EMBO Mol Med |
| Language | eng |
| DOI | 10.15252/emmm.201708076 |
| ISSN | 1757-4684 |
| Library Catalog | PubMed |
| Extra | PMID: 29212784 PMCID: PMC5801506 |
| Tags | antibody therapy, kinase inhibitor, NSCLC, original, T790M, top |
| Date Added | 2018/11/15 - 16:12:45 |
| Date Modified | 2020/01/22 - 08:45:14 |
| Notes and Attachments | Full Text (Attachment) PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
