Harnessing biomarkers to guide immunotherapy in esophageal cancer: toward precision oncology.

Journal: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
Published Date: Sep 6, 2025

Abstract

Esophageal cancer (EC) is one of the most serious health issues around the world, ranking seventh among the most lethal types of cancer and eleventh among the most common types of cancer worldwide. Traditional therapies-such as surgery, chemotherapy, and radiation therapy-often yield limited success, especially in the advanced stages of EC, prompting the pursuit of novel and more effective treatment strategies. Immunotherapy has emerged as a promising option; nonetheless, its clinical success is hindered by variable patient responses. This underscores the urgent need for predictive biomarkers that can identify patients most likely to benefit from immunotherapeutic interventions. Biomarker-based patient stratification can improve treatment outcomes, prevent unnecessary exposures, and conserve healthcare resources. This review explores established and emerging biomarkers for predicting response to immunotherapy in EC. We discuss these biomarkers by categorizing them into four major groups: (i) tumor-related biomarkers (PD-L1 expression, tumor mutational burden, and microsatellite instability), (ii) tumor-immune microenvironment-related biomarkers (tumor-infiltrating lymphocytes and immune cell subtypes and ratios), (iii) blood-based biomarkers (circulating tumor DNA, exosomes, and soluble proteins), and (iv) microbiomes (oral, esophageal, and gut microbiomes). In addition, Advancements in biomarker discovery technologies such as high-throughput sequencing, multi-omics approaches, artificial intelligence and machine learning, single-cell analysis, and liquid biopsy are also discussed for their potential to refine biomarker identification and clinical application.

Authors

  • Amany I Almars
    Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80324, 21589, Jeddah, Saudi Arabia. [email protected].
  • Sameerah Shaheen
    Department of Anatomy and Stem Cell Unit, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
  • Nahlah M Ghouth
    Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, 21955, Makkah, Saudi Arabia.
  • Iman S Abumansour
    Department of Medical Genetics, College of Medicine, Umm Al-Qura University, Mecca, Saudi Arabia.
  • Asim Abdulaziz Khogeer
    Research and Studies Unit, PMO, Makkah Regional Branch, Ministry of Health, Makkah, Saudi Arabia.
  • Fayez Alsulaimani
    Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80324, 21589, Jeddah, Saudi Arabia.
  • Ahmed M Basri
    Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80324, 21589, Jeddah, Saudi Arabia.
  • Nasser A Elhawary
    Department of Medical Genetics, College of Medicine, Umm Al-Qura University, Mecca, Saudi Arabia.
  • Tabinda Hasan
    Department of Anatomy, College of Medicine, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia.
  • Hailah M Almohaimeed
    Department of Basic Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

Keywords

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