Targeting the complexity of ERBB2 biology in gastroesophageal carcinoma.

Augustin, J E; Soussan, P; Bass, A J

Augustin, J E; Soussan, P; Bass, A J.

Afiliación

Augustin JE; Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, USA; Department of Pathology, Henri Mondor University Hospital, Assistance Publique - Hôpitaux de Paris, Créteil, France; INSERM U955 Team 18, Université Paris Est Créteil - Faculté de Médecine, Créteil, France.
Soussan P; Institut National de la Santé et de la Recherche Médicale U938, Centre de Recherche Saint-Antoine, Sorbonne Université - Faculté Saint Antoine, Paris, France; Department of Virology, GHU Paris-Est, Assistance Publique - Hôpitaux de Paris, Paris, France.
Bass AJ; Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, USA; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, USA. Electronic address: ab5147@cumc.columbia.edu.

Ann Oncol ; 33(11): 1134-1148, 2022 11.

Article en En | MEDLINE | ID: mdl-35963482

RESUMEN

ERBB2 is the most prominent therapeutic target in gastroesophageal adenocarcinoma (GEA). For two decades, trastuzumab was the only treatment available for GEA overexpressing ERBB2. Several drugs showing evidence of efficacy over or in complement to trastuzumab in breast cancer failed to show clinical benefit in GEA. This resistance to anti-ERBB2 therapy is peculiarly recurrent in GEA and is mostly due to tumor heterogeneity with the existence of low expressing ERBB2 tumor clones and loss of ERBB2 over time. The development of new ERBB2 testing strategies and the use of antibody-drug conjugates having a bystander effect are providing new tools to fight heterogeneity in ERBB2-positive GEA. Co-amplifications of tyrosine kinase receptors, alterations in mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K) signaling pathways and in proteins controlling cell cycle are well known to contribute resistance to anti-ERBB2 therapy, and they can be targeted by dual therapy. Recently described, NF1 mutations are responsible for Ras phosphorylation and activation and can also be targeted by MEK/ERK inhibition along with anti-ERBB2 therapy. Multiple lines of evidence suggest that immune mechanisms involving antibody-dependent cell-mediated cytotoxicity are preponderant over intracellular signaling in anti-ERBB2 therapy action. A better comprehension of these mechanisms could leverage immune action of anti-ERBB2 therapy and elucidate efficacy of combinations associating immunotherapy and anti-ERBB2 therapy, as suggested by the recent intermediate positive results of the KEYNOTE-811 trial.

Asunto(s)

Adenocarcinoma; Neoplasias de la Mama; Neoplasias Esofágicas; Neoplasias Gástricas; Humanos; Femenino; Receptor ErbB-2/genética; Receptor ErbB-2/metabolismo; Trastuzumab/uso terapéutico; Neoplasias Gástricas/tratamiento farmacológico; Neoplasias Gástricas/genética; Neoplasias Gástricas/patología; Neoplasias Esofágicas/patología; Neoplasias de la Mama/patología; Adenocarcinoma/tratamiento farmacológico; Biología; Línea Celular Tumoral

Palabras clave

ERBB2; antibody-dependent cell-mediated cytotoxicity; antibody-drug conjugates; drug resistance; gastroesophageal adenocarcinoma; immunotherapy

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Neoplasias de la Mama / Neoplasias Esofágicas / Adenocarcinoma Límite: Female / Humans Idioma: En Revista: Ann Oncol Asunto de la revista: NEOPLASIAS Año: 2022 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido

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