Molecular Assessment of HER2 to Identify Signatures Associated with Therapy Response in HER2-Positive Breast Cancer.

Autor: Maddox AL; Department of Molecular Medicine, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA., Brehove MS; Department of Molecular Medicine, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA., Eliato KR; Department of Molecular Medicine, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA., Saftics A; Department of Molecular Medicine, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA., Romano E; Department of Molecular Medicine, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA., Press MF; Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90089, USA., Mortimer J; Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA., Jones V; Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA., Schmolze D; Department of Pathology, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA., Seewaldt VL; Department of Population Sciences, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA., Jovanovic-Talisman T; Department of Molecular Medicine, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2022 Jun 04; Vol. 14 (11). Date of Electronic Publication: 2022 Jun 04.
DOI: 10.3390/cancers14112795
Abstrakt: Trastuzumab, the prototype HER2-directed therapy, has markedly improved survival for women with HER2-positive breast cancers. However, only 40-60% of women with HER2-positive breast cancers achieve a complete pathological response to chemotherapy combined with HER2-directed therapy. The current diagnostic assays have poor positive-predictive accuracy in identifying therapy-responsive breast cancers. Here, we deployed quantitative single molecule localization microscopy to assess the molecular features of HER2 in a therapy-responsive setting. Using fluorescently labeled trastuzumab as a probe, we first compared the molecular features of HER2 in trastuzumab-sensitive (BT-474 and SK-BR-3) and trastuzumab-resistant (BT-474 R and JIMT-1) cultured cell lines. Trastuzumab-sensitive cells had significantly higher detected HER2 densities and clustering. We then evaluated HER2 in pre-treatment core biopsies from women with breast cancer undergoing neoadjuvant therapy. A complete pathological response was associated with a high detected HER2 density and significant HER2 clustering. These results established the nano-organization of HER2 as a potential signature of therapy-responsive disease.
Databáze: MEDLINE
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