---
title: "Antibody-Drug Conjugates for Advanced Esophageal Cancer: Targets, Evidence, and Clinical Integrati"
id: "pubmed-42700288"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42700288"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42700288/"
doi: "10.1007/s11864-026-01411-2"
published_at: "2026-09-05T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Antibody-Drug Conjugates for Advanced Esophageal Cancer: Targets, Evidence, and Clinical Integrati
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42700288
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42700288/)
- **DOI:** [10.1007/s11864-026-01411-2](https://doi.org/10.1007%2Fs11864-026-01411-2)
- **Published At:** 2026-09-05T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Esophageal cancer has high mortality and limited options after progression on first-line **chemoimmunotherapy**; antibody-drug conjugates (**ADCs**) are presented as a promising class for later-line treatment. - ADCs combine the targeting specificity of monoclonal antibodies with potent cytotoxic payloads to enable selective tumor cell killing and potentially reduce off-target toxicity. - For **HER2-positive gastroesophageal junction adenocarcinoma**, the review favors **trastuzumab deruxtecan** based on reported overall survival benefit and a bystander killing effect that may confer activity in **HER2-low** tumors. - In **HER2-negative gastroesophageal adenocarcinoma**, **TROP2** (trophoblast cell-surface antigen 2) is highlighted as a promising target because moderate-to-strong expression occurs in nearly 80% of cases; **sacituzumab tirumotecan** is undergoing phase III evaluation in this population. - For **esophageal squamous cell carcinoma (ESCC)**, biomarker-guided ADC selection is recommended. **B7-H3** is overexpressed in >90% of ESCC and supports B7-H3–directed ADC strategies. - **Nectin-4** expression allows consideration of **enfortumab vedotin** as a later-line option, though activity is described as modest. - A bispecific ADC targeting both **EGFR** and **HER3** (BL-B01D1) has shown notable efficacy in immunotherapy-refractory ESCC and is described as a breakthrough in that subtype. - For **CLDN18.2-positive** gastroesophageal junction adenocarcinoma, several ADCs (CMG901, IBI343, tecotabart vedotin) are identified as promising later-line options. - Patient selection should rely on validated predictive biomarkers and treatment choice must consider distinct toxicity profiles; **interstitial lung disease** (ILD) is specifically noted as an important toxicity with trastuzumab deruxtecan. - The authors support moving ADCs earlier in the treatment course and into perioperative settings through well-designed clinical trials to improve long-term outcomes.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Department of Oncology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China. * 2 Department of Oncology, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, China. * 3 College of Pharmacy, Dalian Medical University, Dalian, China. * 4 Medical Research Department, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, China. zhuwj@uhrs.edu.cn. * 5 Department of Oncology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China. 290821357@qq.com. * 6 Department of Oncology, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, China. 290821357@qq.com. * PMID: **42700288** * DOI: [ 10.1007/s11864-026-01411-2 ](https://doi.org/10.1007/s11864-026-01411-2) Item in Clipboard Review # Antibody-Drug Conjugates in the Treatment of Esophageal Cancer Dapeng Wu et al. Curr Treat Options Oncol. 2026. Show details Display options Display options Format Abstract PubMed PMID Curr Treat Options Oncol Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Curr+Treat+Options+Oncol%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Curr+Treat+Options+Oncol%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700288/) . 2026 Sep 5;27(1):46. doi: 10.1007/s11864-026-01411-2. ### Authors [Dapeng Wu](https://pubmed.ncbi.nlm.nih.gov/?term=Wu+D&cauthor_id=42700288)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42700288/#short-view-affiliation-1 "Department of Oncology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42700288/#short-view-affiliation-2 "Department of Oncology, Qingdao Hospital, University of Health and Rehabilitation Sciences \(Qingdao Municipal Hospital\), Qingdao, China."), [Wei Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+W&cauthor_id=42700288)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42700288/#short-view-affiliation-1 "Department of Oncology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42700288/#short-view-affiliation-2 "Department of Oncology, Qingdao Hospital, University of Health and Rehabilitation Sciences \(Qingdao Municipal Hospital\), Qingdao, China."), [Qi Zhao](https://pubmed.ncbi.nlm.nih.gov/?term=Zhao+Q&cauthor_id=42700288)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42700288/#short-view-affiliation-3 "College of Pharmacy, Dalian Medical University, Dalian, China."), [Wenjing Zhu](https://pubmed.ncbi.nlm.nih.gov/?term=Zhu+W&cauthor_id=42700288)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42700288/#short-view-affiliation-4 "Medical Research Department, Qingdao Hospital, University of Health and Rehabilitation Sciences \(Qingdao Municipal Hospital\), Qingdao, China. zhuwj@uhrs.edu.cn."), [Jian Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+J&cauthor_id=42700288)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42700288/#short-view-affiliation-5 "Department of Oncology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China. 290821357@qq.com.")[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42700288/#short-view-affiliation-6 "Department of Oncology, Qingdao Hospital, University of Health and Rehabilitation Sciences \(Qingdao Municipal Hospital\), Qingdao, China. 290821357@qq.com.") ### Affiliations * 1 Department of Oncology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China. * 2 Department of Oncology, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, China. * 3 College of Pharmacy, Dalian Medical University, Dalian, China. * 4 Medical Research Department, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, China. zhuwj@uhrs.edu.cn. * 5 Department of Oncology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China. 290821357@qq.com. * 6 Department of Oncology, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, China. 290821357@qq.com. * PMID: **42700288** * DOI: [ 10.1007/s11864-026-01411-2 ](https://doi.org/10.1007/s11864-026-01411-2) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract Esophageal cancer remains one of the most lethal malignancies worldwide, with particularly poor outcomes following disease progression after first-line chemoimmunotherapy. Antibody-drug conjugates (ADCs) have emerged as a transformative therapeutic class that combines the targeting precision of monoclonal antibodies with potent cytotoxic payloads, enabling selective tumor cell killing while minimizing off-target toxicity. In the management of advanced esophageal cancer, I advocate for the integration of ADCs as a therapeutic option following progression on first-line chemoimmunotherapy. For patients with human epidermal growth factor receptor 2 (HER2)-positive gastroesophageal junction adenocarcinoma, trastuzumab deruxtecan is my preferred choice based on its superior overall survival benefit and robust bystander killing effect, which also confers activity in HER2-low tumors. For HER2-negative gastroesophageal adenocarcinoma, trophoblast cell-surface antigen 2 represents a promising target given its high prevalence of moderate to strong expression in nearly 80% of cases, and sacituzumab tirumotecan is currently under phase III investigation in this setting. In esophageal squamous cell carcinoma, I recommend biomarker-guided selection among ADCs targeting B7-H3, given its overexpression in over 90% of cases. For Nectin-4-expressing tumors, enfortumab vedotin may be considered as a later-line alternative despite modest activity. Notably, the bispecific ADC targeting both epidermal growth factor receptor and human epidermal growth factor receptor 3, BL-B01D1, has demonstrated compelling efficacy in immunotherapy-refractory esophageal squamous cell carcinoma, and I consider it a breakthrough option in this subtype. For claudin-18.2-positive gastroesophageal junction adenocarcinoma, several ADCs including CMG901, IBI343, and tecotabart vedotin represent promising later-line choices. I emphasize that patient selection should be guided by validated predictive biomarkers, and treatment decisions must account for distinctive toxicity profiles, particularly interstitial lung disease with trastuzumab deruxtecan. Finally, I strongly support advancing ADCs into earlier lines of therapy and perioperative settings through well-designed clinical trials to further improve long-term outcomes in this aggressive malignancy. **Keywords:** Antibody–drug conjugate; B7-H3; CLDN18.2; Esophageal cancer; HER2; TROP2. © 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors. Conflict of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## References 1. 1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–63. - [PubMed](https://pubmed.ncbi.nlm.nih.gov/38572751/) 2. 1. Morgan E, Soerjomataram I, Rumgay H, et al. The Global Landscape of Esophageal Squamous Cell Carcinoma and Esophageal Adenocarcinoma Incidence and Mortality in 2020 and Projections to 2040: New Estimates From GLOBOCAN 2020. Gastroenterology. 2022;163(3):649–e6582. - [PubMed](https://pubmed.ncbi.nlm.nih.gov/35671803/) - [DOI](https://doi.org/10.1053/j.gastro.2022.05.054) 3. 1. Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025;75(1):10–45. - [PubMed](https://pubmed.ncbi.nlm.nih.gov/39817679/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/11745215/) 4. 1. Sun JM, Shen L, Shah MA, et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021;398(10302):759–71. - [PubMed](https://pubmed.ncbi.nlm.nih.gov/34454674/) - [DOI](https://doi.org/10.1016/s0140-6736\(21\)01234-4) 5. 1. Doki Y, Ajani JA, Kato K, et al. Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. N Engl J Med. 2022;386(5):449–62. - [PubMed](https://pubmed.ncbi.nlm.nih.gov/35108470/) - [DOI](https://doi.org/10.1056/nejmoa2111380) Show all 80 references ## Publication types * Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700288/) ## MeSH terms * Antineoplastic Agents, Immunological* / therapeutic use Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Antineoplastic+Agents%2C+Immunological%2Ftherapeutic+use%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Antineoplastic+Agents%2C+Immunological) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700288/) * Biomarkers, Tumor Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Biomarkers%2C+Tumor%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Biomarkers%2C+Tumor) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700288/) * Erb-b2 Receptor Tyrosine Kinases / antagonists & inhibitors Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Erb-b2+Receptor+Tyrosine+Kinases%2Fantagonists+and+inhibitors%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Erb-b2+Receptor+Tyrosine+Kinases) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700288/) * Erb-b2 Receptor Tyrosine Kinases / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Erb-b2+Receptor+Tyrosine+Kinases%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Erb-b2+Receptor+Tyrosine+Kinases) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700288/) * Esophageal Neoplasms* / diagnosis Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Esophageal+Neoplasms%2Fdiagnosis%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Esophageal+Neoplasms) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700288/) * Esophageal Neoplasms* / drug therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Esophageal+Neoplasms%2Fdrug+therapy%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Esophageal+Neoplasms) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700288/) * Esophageal Neoplasms* / etiology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Esophageal+Neoplasms%2Fetiology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Esophag
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