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Review
. 2024 Nov;26(11):1469-1488.
doi: 10.1007/s11912-024-01607-5. Epub 2024 Oct 23.

Evolving Treatment Landscape for Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma

Margaret C Wheless  1 , Margaret Comer  2 , Michael K Gibson  3   4
Affiliations
Review

Evolving Treatment Landscape for Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma

Margaret C Wheless et al. Curr Oncol Rep. 2024 Nov.

Abstract

Purpose of review: This review highlights advances and recent changes in the treatment paradigm for advanced esophageal adenocarcinoma (EAC) and gastroesophageal junction adenocarcinoma (GEJAC).

Recent findings: Chemotherapy remains the backbone of treatment for advanced EAC/GEJAC. New targets/agents include immunotherapy, HER-2, claudin18.2, and FGFR2b, with various mechanisms (CAR-T, bispecific mAB, ADCs) altering the treatment landscape against these targets. The approaches to these targets may act together, in sequence, and even synergistically to improve outcomes. Herein, we review the state of the field, including highlighting ongoing clinical trials and additional emerging agents and approaches.

Keywords: Claudin18.2; Esophageal Adenocarcinoma; FGFR; Gastroesophageal Junction Adenocarcinoma; HER-2; PD-L1 Therapy.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. 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.

Figures

Fig. 1
Fig. 1
Mechanism of Novel Therapeutics displays the different mechanisms of action of drug targets in development for gastroesophageal adenocarcinoma. Bispecific antibodies (1) join specific cancer antigens, such as CLDN18.2 and HER-2, to cytotoxic T-cells for destruction. Destruction by T-cells and NK cells via ADCC (4) leads to the release of cancer antigens which further stimulate the immune response within the tumor microenvironment (2). Antibody drug conjugates (3) are tumor-targeted antibodies attached to a cytotoxic payload which poisons both the antigen-expressing cells and neighboring cancer cells. Targeted monoclonal antibodies and TKIs (5) inhibit tumorigenesis by blocking proliferative cellular pathways. CAR-T (6) allows cytotoxic T-cells to directly recognize cancer antigens via the TCR, causing activation and proliferation of cytotoxic CAR-Ts for tumor destruction. Lastly, immune checkpoint inhibition (7) via CTLA-4, PD1/PD-L1, and TIGIT allows for enhanced immune recognition of tumor cells. Abbreviations: ADC, antibody drug conjugate; ADCC, antibody-dependent cellular cytotoxicity; CAR-T, chimeric antigen receptor T-cell; CLDN18.2, claudin18.2; mAb, monoclonal antibody; TKI, tyrosine kinase inhibitor. Created with BioRender.com
See this image and copyright information in PMC

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