双重HER2阻断期间和之后HER2阳性乳腺癌的表型变化。,Nature Communications

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双重HER2阻断期间和之后HER2阳性乳腺癌的表型变化。
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-20 , DOI: 10.1038/s41467-019-14111-3
Fara Brasó-Maristany _{1,

2} , Gaia Griguolo _{1,

2,

3,

4} , Tomás Pascual _{1,

2,

5} , Laia Paré ₅ , Paolo Nuciforo _{6,

7} , Antonio Llombart-Cussac ₈ , Begoña Bermejo ₉ , Mafalda Oliveira _{6,

7} , Serafín Morales ₁₀ , Noelia Martínez ₁₁ , Maria Vidal _{1,

2,

5} , Barbara Adamo _{1,

2} , Olga Martínez _{1,

2} , Sonia Pernas _{5,

12} , Rafael López ₁₃ , Montserrat Muñoz _{1,

2} , Núria Chic _{1,

2} , Patricia Galván _{1,

2} , Isabel Garau ₁₄ , Luis Manso ₁₅ , Jesús Alarcón ₁₆ , Eduardo Martínez ₁₇ , Sara Gregorio ₁₈ , Roger R Gomis ₁₈ , Patricia Villagrasa ₅ , Javier Cortés _{7,

19} , Eva Ciruelos _{5,

15} , Aleix Prat _{1,

2,

5}

Affiliation

Department of Medical Oncology, Hospital Clínic de Barcelona, Carrer de Villarroel, 170, 08036, Barcelona, Spain.
Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Carrer del Rosselló, 149-153, 08036, Barcelona, Spain.
Department of Surgery, Oncology and Gastroenterology, University of Padova, Via Giustiniani, 2, 35124, Padova, Italy.
Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Via Gattamelata, 64, 35128, Padova, Italy.
SOLTI Breast Cancer Research Group, Carrer de Balmes, 115, 08008, Barcelona, Spain.
Vall d'Hebrón University Hospital, Passeig de la Vall d'Hebron, 119-129, 08035, Barcelona, Spain.
Vall d´Hebron Institute of Oncology (VHIO), Carrer de Natzaret, 115-117, 08035, Barcelona, Spain.
Hospital Universitario Arnau de Vilanova, Carrer de Sant Clement, 12, 46015, Valencia, Spain.
Hospital Clínico Universitario de Valencia, Av. de Blasco Ibáñez, 17, 46010, Valencia, Spain.
Hospital Universitario Arnau de Vilanova, Av. Alcalde Rovira Roure, 80, 25198, Lleida, Spain.
Hospital Universitario Ramón y Cajal, M-607, km. 9, 100, 28034, Madrid, Spain.
Institut Catala d'Oncologia, Avinguda de la Gran Via de l'Hospitalet, 199-203, 08908, Hospitalet de Llobregat, Spain.
Hospital Clínico Universitario de Santiago, Rúa da Choupana, s/n, 15706, Santiago de Compostela, Spain.
Hospital Son Llàtzer, Ctra. de Manacor, 07198, Palma de Mallorca, Spain.
Hospital Universitario 12 de Octubre, Av. de Córdoba, s/n, 28041, Madrid, Spain.
Hospital Universitario Son Espases, Carretera de Valldemossa, 79, 07120, Palma de Mallorca, Spain.
Consorcio Hospitalario Provincial de Castellón, Av. del Dr. Clarà, 19, 12002, Castellón de la Plana, Spain.
Institute for Research in Biomedicine, Carrer de Baldiri Reixac, 10, 08028, Barcelona, Spain.
IOB Institute of Oncology, Quiron Group, Plaça d'Alfonso Comín, 5, 08023, Barcelona, Spain.

HER2阳性（HER2 +）乳腺癌中富含HER2的亚型（HER2-E）对HER2途径高度依赖。但是，约有20-60％的HER2 + / HER2-E肿瘤在抗HER2治疗后无法完全缓解。在这里，我们评估了拉美替尼和曲妥珠单抗新辅助治疗之前，期间和之后在PAMELA试验和乳腺癌细胞系的HER2 + / HER2-E肿瘤中的基因表达数据。我们的结果表明，HER2-E疾病的双重HER2阻断在患者的肿瘤和体外模型中均诱导了低增殖的Luminal A表型。与HR阴性疾病相比，这些生物学变化在激素受体阳性（HR +）疾病中更为明显。有趣的是，用抗HER2疗法增加管腔表型增加了对CDK4 / 6抑制的敏感性。最后，体外终止HER2靶向治疗或获得抗HER2治疗耐药性可恢复原始HER2-E表型。我们的发现支持维持性抗HER2治疗的使用以及CDK4 / 6抑制亚型转换的治疗性利用。

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更新日期：2020-01-22

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