ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicDeciphering the Inflammatory Response in Colorectal and Ovarian CancersView all 5 articles
ctDNA guided management of POLE mutant GI malignancies promotes exceptional responses and prolonged survival to immunotherapy
Provisionally accepted
Umair Mahmood1
Chetan Bhan1,2
Charles Imber2Jamie Murphy2Krishna Menon2
Tara Berwick3Zahir Amin1,4
Khurum Hayat Khan1,3,4*- 1University College London Hospitals NHS Foundation Trust, London, United Kingdom
- 2Cleveland Clinic London Ltd, London, United Kingdom
- 3The London Clinic, London, United Kingdom
- 4HCA Healthcare UK, London, United Kingdom
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Patients with unresectable Gastrointestinal cancers (GI) including advanced colorectal cancer (CRC) and gall bladder cancer (GBC) have limited treatment options. Treatment with chemotherapy is associated with limited success resulting from therapeutic resistance. Immune checkpoint inhibitors are effective for a subset of metastatic CRC (5% with MSI-H status) and up to 30% of patients with GBC. Therefore, there is an urgent unmet need to discover new predictive biomarkers to aid patient selection for ICIs with a demonstrated clinical value in a challenging patient population. We highlight the utility of a liquid biopsy approach to aid selection of GI cancer patients harbouring rare POLE mutations for immunotherapy, leading to complete metabolic response in addition to radiologic responses and extended survival in all three patients. This study advocates for specialised multi-disciplinary teams performing shared clinical decision making to advance personalised care and improve outcomes of a subset of GI cancer patients with a poor prognosis.
Keywords: colorectal cancer, CtDNA, Gall bladder cancer, Immunotherapy, pole
Received: 03 Nov 2025; Accepted: 02 Feb 2026.
Copyright: © 2026 Mahmood, Bhan, Imber, Murphy, Menon, Berwick, Amin and Khan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Khurum Hayat Khan
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