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Human epidermal growth factor receptor 2 (HER2) was the first molecule targeted by monoclonal antibodies in solid disease. Interestingly, the first patients with disseminated HER2-positive metastatic breast cancer who received the anti-HER2 drug trastuzumab in phase I trials in the early 1990s are still alive (Siddhartha Mukharjee, The Emperor of All Maladies, A Biography of Cancer, Scribner, New York, NY, USA). This opened the door for several investigations to identify other biomarkers for targeted therapies, which significantly changed the treatment armamentarium of several types of cancer.
In the case of HER2, gastroesophageal adenocarcinoma also showed a subset of positivity, making this disease a good candidate for anti-HER2 treatments. Thus, the initial results of the TOGA trial were celebrated in the gastrointestinal oncology community as the anti-HER2 drug trastuzumab demonstrated efficacy in this entity in addition to breast cancer [1].
Therefore, HER2 assessments and trastuzumab treatment became inevitable standards in gastroesophageal cancers. After that, there were major attempts to find new drugs for different settings of treatment of gastric and esophageal adenocarcinoma. The mini-review by Ilhan-Mutlu et al. describes the past of anti-HER2 treatment, the current standard strategy and the future perspective for gastroesophageal tumors [2]. HER2-positive patients with gastroesophageal adenocarcinoma may have a unique disease course due to in some part slow progression of the disease. The case report by Roider-Schur et al. confirms this suggestion and shows an interesting case with many learning effects [3].
We hope that readers of this issue will find the articles interesting and will be able to collect relevant data for everyday clinical practice.
References
Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687-97.
Ilhan-Mutlu A. Second line treatment of HER2 positive advanced gastroesophageal adenocarcinoma: past, present and future. memo. 2023;16(4).
Roider-Schur S, Machat S, Öhler L. Fast and significant response to Her2-directed therapy in the 5th line in a patient with HER2-positive metastatic adenocarcinoma of the gastroesophageal junction—A case report. memo. 2023;16(3).
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A. Ilhan-Mutlu: Participation in advisory boards organized by MSD, Servier, Daiichi Sankyo, BMS and Astellas, lecture honoraria from Eli Lilly, Servier, BMS, MSD, Astellas and Daiichi Sankyo, consulting for Astellas, MSD, Amgen and Astra Zeneca, travel support from BMS, Roche, Eli Lilly and Daiichi Sankyo.
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Ilhan-Mutlu, A. HER2 in focus—gastric cancer. memo 16, 217 (2023). https://doi.org/10.1007/s12254-023-00925-x
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DOI: https://doi.org/10.1007/s12254-023-00925-x