Cartwright, Douglas and Kidd, Andrew C. and Ansel, Sonam and Ascierto, Maria Libera and Spiliopoulou, Pavlina (2025) Oncogenic signalling pathways in cancer immunotherapy: leader or follower in this delicate dance? International Journal of Molecular Sciences, 26 (9): 4393. ISSN 1661-6596

Abstract

Immune checkpoint inhibitors have become a mainstay of treatment in many solid organ malignancies. Alongside this has been the rapid development in the identification and targeting of oncogenic drivers. The presence of alterations in oncogenic drivers not only predicts response to target therapy but can modulate the immune microenvironment and influence response to immunotherapy. Combining immune checkpoint inhibitors with targeted agents is an attractive therapeutic option but overlapping toxicity profiles may limit the clinical use of some combinations. In addition, there is growing evidence of shared resistance mechanisms that alter the response to immunotherapy when it is used after targeted therapy. Understanding this complex interaction between oncogenic drivers, targeted therapy and response to immune checkpoint inhibitors is vital for selecting the right treatment, at the right time for the right patient. In this review, we summarise the preclinical and clinical evidence of the influence of four common oncogenic alterations on immune checkpoint inhibitor response, combination therapies, and the presence of shared resistance mechanisms. We highlight the common resistance mechanisms and the need for more randomised trials investigating both combination and sequential therapy.

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Cartwright, D.
Author

Cartwright, Douglas and Kidd, Andrew C. and Ansel, Sonam and Ascierto, Maria Libera and Spiliopoulou, Pavlina (2025) Oncogenic signalling pathways in cancer immunotherapy: leader or follower in this delicate dance? International Journal of Molecular Sciences, 26 (9): 4393. ISSN 1661-6596

Peters, A.L. and Hall, P.S. and Jordan, L.B. and Soh, F.Y. and Hannington, L. and Makaranka, S. and Urquhart, G. and Vallet, M. and Cartwright, D. and Marashi, H. and Elsberger, B. (2024) Enhancing clinical decision support with genomic tools in breast cancer: a Scottish perspective. Breast, 75: 103728. ISSN 0960-9776

Neilson, Lisa J. and Cartwright, Douglas and Risteli, Maija and Jokinen, Elina M. and McGarry, Lynn and Sandvik, Toni and Nikolatou, Konstantina and Hodge, Kelly and Atkinson, Samuel and Vias, Maria and Kay, Emily J. and Brenton, James D. and Carlin, Leo M. and Bryant, David M. and Salo, Tuula and Zanivan, Sara (2023) Omentum-derived matrix enables the study of metastatic ovarian cancer and stromal cell functions in a physiologically relevant environment. Matrix Biology Plus, 19-20: 100136. ISSN 2590-0285

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Kidd, Andrew C.
Author

Cartwright, Douglas and Kidd, Andrew C. and Ansel, Sonam and Ascierto, Maria Libera and Spiliopoulou, Pavlina (2025) Oncogenic signalling pathways in cancer immunotherapy: leader or follower in this delicate dance? International Journal of Molecular Sciences, 26 (9): 4393. ISSN 1661-6596

Kidd, Andrew C. and Cowell, Gordon W. and Martin, Geoffrey A. and Ferguson, Jenny and Fennell, Dean A. and Evison, Matt and Blyth, Kevin G. (2024) The prevalence and prognostic significance of sarcopenia and adipopenia in pleural mesothelioma. Cancer Treatment and Research Communications, 42: 100856. ISSN 2468-2942

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Ansel, Sonam
Author

Cartwright, Douglas and Kidd, Andrew C. and Ansel, Sonam and Ascierto, Maria Libera and Spiliopoulou, Pavlina (2025) Oncogenic signalling pathways in cancer immunotherapy: leader or follower in this delicate dance? International Journal of Molecular Sciences, 26 (9): 4393. ISSN 1661-6596

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Ascierto, Maria Libera
Author

Cartwright, Douglas and Kidd, Andrew C. and Ansel, Sonam and Ascierto, Maria Libera and Spiliopoulou, Pavlina (2025) Oncogenic signalling pathways in cancer immunotherapy: leader or follower in this delicate dance? International Journal of Molecular Sciences, 26 (9): 4393. ISSN 1661-6596

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Spiliopoulou, Pavlina
Author

Cartwright, Douglas and Kidd, Andrew C. and Ansel, Sonam and Ascierto, Maria Libera and Spiliopoulou, Pavlina (2025) Oncogenic signalling pathways in cancer immunotherapy: leader or follower in this delicate dance? International Journal of Molecular Sciences, 26 (9): 4393. ISSN 1661-6596

Genta, S. and Araujo, D.V. and Hueniken, K. and Pipinikas, C. and Ventura, R. and Rojas, P. and Jones, G. and Butler, M.O. and Saibil, S.D. and Yu, C. and Easson, A. and Covelli, A. and Sauder, M.B. and Fournier, C. and Saeed Kamil, Z. and Rogalla, P. and Arteaga, D.P. and Vornicova, O. and Spiliopoulou, Pavlina and Muniz, T.P. and Siu, L.L. and Spreafico, A. (2024) Bespoke ctDNA for longitudinal detection of molecular residual disease in high-risk melanoma patients. ESMO Open, 9 (11): 103978. ISSN 2059-7029

Spear, Sarah and Le Saux, Olivia and Mirza, Hasan B. and Iyer, Nayana and Tyson, Katie and Grundland Freile, Fabio and Walton, Josephine B. and Woodman, Chloe and Jarvis, Sheba and Ennis, Darren P. and Aguirre Hernandez, Carmen and Xu, Yuewei and Spiliopoulou, Pavlina and Brenton, James D. and Costa-Pereira, Ana P. and Cook, David P. and Vanderhyden, Barbara C. and Keun, Hector C. and Triantafyllou, Evangelos and Arnold, James N. and McNeish, Iain A. (2024) PTEN loss shapes macrophage dynamics in high grade serous ovarian carcinoma. Cancer Research. ISSN 0008-5472 (In Press)

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