Resistance to immune checkpoint inhibitors in advanced gastro-oesophageal cancers

Mark A. Baxter (Lead / Corresponding author), Fearghas Middleton, Hannah P. Cagney, Russell D. Petty (Lead / Corresponding author)

Research output: Contribution to journalReview articlepeer-review

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Abstract

Immune checkpoint inhibitors (ICIs) have altered the treatment paradigm across a range of tumour types, including gastro-oesophageal cancers. For patients with any cancer type who respond, ICIs can confer long-term disease control and significantly improve survival and quality of life, but for patients with gastro-oesophageal cancer, ICIs can be transformative, as durable responses in advanced disease have hitherto been rare, especially in those patients who are resistant to first-line cytotoxic therapies. Results from trials in patients with advanced-stage gastro-oesophageal cancer have raised hopes that ICIs will be successful as adjuvant and neoadjuvant treatments in early-stage disease, when the majority of patients relapse after potential curative treatments, and several trials are ongoing. Unfortunately, however, ICI-responding patients appear to constitute a minority subgroup within gastro-oesophageal cancer, and resistance to ICI therapy (whether primary or acquired) is common. Understanding the biological mechanisms of ICI resistance is a current major research challenge and involves investigation of both tumour and patient-specific factors. In this review, we discuss the mechanisms underlying ICI resistance and their potential specific applications of this knowledge towards precision medicine strategies in the management of gastro-oesophageal cancers in clinical practice.

Original languageEnglish
Number of pages12
JournalBritish Journal of Cancer
Early online date6 Jul 2021
DOIs
Publication statusE-pub ahead of print - 6 Jul 2021

Keywords

  • Gastric cancer
  • Oesophageal cancer

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