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Current status and future perspectives in HER2 positive advanced gastric cancer

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Abstract

Gastric cancer is one of the most common malignancy worldwide with a prognosis less than 1 year in unresectable or metastatic disease. HER2 expression is the main biomarker to lead the addition of trastuzumab to first line systemic chemotherapy improving the overall survival in advanced HER2-positivegastric adenocarcinoma. The inevitable development of resistance to trastuzumab remains a great problem inasmuch several treatment strategies that have proven effective in breast cancer failed to show clinical benefit in advanced gastric cancer. In this review, we summarize the available data on the mechanisms underlying primary and secondary resistance toHER2-targeted therapy and current challenges in the treatment of HER2-positive advanced gastric cancer refractory to trastuzumab. Further, we describe the prognostic value of new non-invasive screening techniques, the current development of novel agents such us HER2 antibody–drug conjugates and bispecific antibodies, and the strategies with antitumor activity on going.

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  1. Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy

    G. Roviello

  2. School of Human Health Sciences, University of Florence, Largo Brambilla 3, 50134, Florence, Italy

    M. Catalano

  3. Department of Health Science, University “Magna Graecia” of Catanzaro, Catanzaro, Italy

    L. F. Iannone

  4. Department of Medical, Surgical and NeuroSciences, Section of Surgery, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy

    L. Marano

  5. Clinical Oncology Unit, Careggi University Hospital, Florence, Italy

    M. Brugia & G. Rossi

  6. Department of Oncology, San Bortolo General Hospital, AULSS8 Berica, Vicenza, Italy

    G. Aprile

  7. Department of Experimental and Clinical Medicine, University of Florence, 50134, Florence, Italy

    L. Antonuzzo

  8. Medical Oncology Unit, Careggi University Hospital, 50134, Florence, Italy

    L. Antonuzzo

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Roviello, G., Catalano, M., Iannone, L.F. et al. Current status and future perspectives in HER2 positive advanced gastric cancer. Clin Transl Oncol 24, 981–996 (2022). https://doi.org/10.1007/s12094-021-02760-0

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