Can Liquid Biopsy Predict the Future of a Tumour? A Critical Review of AI-Enabled Longitudinal Modelling for Cancer Evolution and Treatment Resistance
Oncology, Nuclear Medicine and Transplantology, 2(4), 2026, onmt029, https://doi.org/10.63946/onmt/19502
Publication date: Oct 06, 2026
ABSTRACT
Cancer behaves as a dynamic evolutionary system, whereas conventional tissue biopsy and imaging provide incomplete temporal information about how a tumour is changing. This review critically examines whether longitudinal liquid-biopsy measurement, combined with artificial intelligence (AI), can move oncology from tumour monitoring toward genuine prediction of cancer evolution and treatment resistance. We synthesise mechanistic, clinical, and computational evidence on circulating tumour DNA, circulating tumour cells, extracellular vesicles, and multimodal liquid-biopsy platforms, together with AI approaches applied to longitudinal cancer data, drawing on landmark and recent studies across colorectal, lung, breast, and ovarian cancer. Current evidence distinguishes three increasingly demanding tasks: early detection, longitudinal monitoring, and genuine forecasting. Longitudinal circulating tumour DNA analysis can detect molecular progression and emerging resistance mutations months before radiographic progression, and machine-learning models can stratify survival using serial biomarker metrics; however, most published "AI prediction" studies demonstrate earlier detection or prognostic association rather than prospectively validated forecasting of a future, patient-specific event. Biological variability in tumour shedding, analytical noise, small and irregularly sampled longitudinal datasets, overfitting, data leakage, weak external validation, and limited interpretability constrain the transition from detection to actionable prediction. AI-enabled liquid biopsy has genuine potential to forecast tumour trajectories, but current evidence is considerably stronger for molecular monitoring and early detection than for prospectively validated, clinically actionable prediction. Realising this potential will require standardised assays, prospective longitudinal cohorts with predefined prediction horizons, rigorous external and temporal validation, calibrated and interpretable models, and interventional trials linking predictions to treatment decisions before AI-enabled liquid biopsy can be considered ready to guide clinical care.
KEYWORDS
Liquid Biopsy Circulating Tumour DNA Artificial Intelligence Machine Learning Tumour Evolution Treatment Resistance Longitudinal Monitoring Precision Oncology
CITATION (Vancouver)
Osei RA, Taiye DS, Nwajiugo GK, Oluwaniran O, Muhammed I. Can Liquid Biopsy Predict the Future of a Tumour? A Critical Review of AI-Enabled Longitudinal Modelling for Cancer Evolution and Treatment Resistance. Oncology, Nuclear Medicine and Transplantology. 2026;2(4):onmt029. https://doi.org/10.63946/onmt/19502
APA
Osei, R. A., Taiye, D. S., Nwajiugo, G. K., Oluwaniran, O., & Muhammed, I. (2026). Can Liquid Biopsy Predict the Future of a Tumour? A Critical Review of AI-Enabled Longitudinal Modelling for Cancer Evolution and Treatment Resistance. Oncology, Nuclear Medicine and Transplantology, 2(4), onmt029. https://doi.org/10.63946/onmt/19502
Harvard
Osei, R. A., Taiye, D. S., Nwajiugo, G. K., Oluwaniran, O., and Muhammed, I. (2026). Can Liquid Biopsy Predict the Future of a Tumour? A Critical Review of AI-Enabled Longitudinal Modelling for Cancer Evolution and Treatment Resistance. Oncology, Nuclear Medicine and Transplantology, 2(4), onmt029. https://doi.org/10.63946/onmt/19502
AMA
Osei RA, Taiye DS, Nwajiugo GK, Oluwaniran O, Muhammed I. Can Liquid Biopsy Predict the Future of a Tumour? A Critical Review of AI-Enabled Longitudinal Modelling for Cancer Evolution and Treatment Resistance. Oncology, Nuclear Medicine and Transplantology. 2026;2(4), onmt029. https://doi.org/10.63946/onmt/19502
Chicago
Osei, Richard Afriyie, Danmegoro Suleman Taiye, Godwin Kenechukwu Nwajiugo, Oluwabukunmi Oluwaniran, and Ismaila Muhammed. "Can Liquid Biopsy Predict the Future of a Tumour? A Critical Review of AI-Enabled Longitudinal Modelling for Cancer Evolution and Treatment Resistance". Oncology, Nuclear Medicine and Transplantology 2026 2 no. 4 (2026): onmt029. https://doi.org/10.63946/onmt/19502
MLA
Osei, Richard Afriyie et al. "Can Liquid Biopsy Predict the Future of a Tumour? A Critical Review of AI-Enabled Longitudinal Modelling for Cancer Evolution and Treatment Resistance". Oncology, Nuclear Medicine and Transplantology, vol. 2, no. 4, 2026, onmt029. https://doi.org/10.63946/onmt/19502
REFERENCES
- Nowell PC. The clonal evolution of tumor cell populations. Science. 1976;194(4260):23-8. doi:10.1126/science.959840
- McGranahan N, Swanton C. Clonal heterogeneity and tumor evolution: past, present, and the future. Cell. 2017;168(4):613-28. doi:10.1016/j.cell.2017.01.018
- Dagogo-Jack I, Shaw AT. Tumour heterogeneity and resistance to cancer therapies. Nat Rev Clin Oncol. 2018;15(2):81-94. doi:10.1038/nrclinonc.2017.166
- Siravegna G, Marsoni S, Siena S, Bardelli A. Integrating liquid biopsies into the management of cancer. Nat Rev Clin Oncol. 2017;14(9):531-48. https://doi.org/10.1038/nrclinonc.2017.14
- Wan JCM, Massie C, Garcia-Corbacho J, Mouliere F, Brenton JD, Caldas C, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17(4):223-38. doi:10.1038/nrc.2017.7
- Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224):224ra24.
- Alix-Panabières C, Pantel K. Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov. 2016;6(5):479-91. https://doi.org/10.1158/2159-8290.CD-15-1483
- Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, et al. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell. 2014;158(5):1110-22. https://doi.org/10.1016/j.cell.2014.07.013
- Gremmelspacher D, Gawron J, Szczerba BM, Jahn K, Castro-Giner F, Kuipers J, et al. Phylogenetic inference reveals clonal heterogeneity in circulating tumor cell clusters. Nat Genet. 2025;57(6):1357-61. https://doi.org/10.1038/s41588-025-02205-2
- Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367(6478):eaau6977. doi:10.1126/science.aau6977
- Zhang Y, Sun B, Yu Y, Lu J, Lou Y, Qian F, et al. Multimodal fusion of liquid biopsy and CT enhances differential diagnosis of early-stage lung adenocarcinoma. NPJ Precis Oncol. 2024;8:47. https://doi.org/10.1038/s41698-024-00551-8
- Cohen JD, Li L, Wang Y, Thoburn C, Afsari B, Danilova L, et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science. 2018;359(6378):926-30. https://doi.org/10.1126/science.aar3247
- Rajkomar A, Dean J, Kohane I. Machine learning in medicine. N Engl J Med. 2019;380(14):1347-58. doi:10.1056/NEJMra1814259
- Hochreiter S, Schmidhuber J. Long short-term memory. Neural Comput. 1997;9(8):1735-80. doi:10.1162/neco.1997.9.8.1735
- Vaswani A, Shazeer N, Parmar N, Uszkoreit J, Jones L, Gomez AN, et al. Attention is all you need. In: Advances in Neural Information Processing Systems 30 (NeurIPS 2017). 2017:5998-6008.
- Kim ST, Lee WS, Lanman RB, Mortimer S, Zill OA, Kim KM, et al. Dynamic changes in longitudinal circulating tumour DNA profile during metastatic colorectal cancer treatment. Br J Cancer. 2022;127(4):661-9. https://doi.org/10.1038/s41416-022-01837-z
- Assaf ZJ, Zou W, Fine AD, Socinski MA, Young A, Lloyd A, et al. A longitudinal circulating tumor DNA-based model associated with survival in metastatic non-small-cell lung cancer. Nat Med. 2023;29(4):859-68. https://doi.org/10.1038/s41591-023-02226-6
- Zheng D, Ye X, Zhang MZ, Sun Y, Wang JY, Ni J, et al. Plasma EGFR T790M ctDNA status is associated with clinical outcome in advanced NSCLC patients with acquired EGFR-TKI resistance. Sci Rep. 2016;6:20913. https://doi.org/10.1038/srep20913
- Remon J, Besse B, Ponce Aix S, Callejo A, Al-Rabi K, Bernabe R, et al. Osimertinib treatment based on plasma T790M monitoring in patients with EGFR-mutant non-small-cell lung cancer (NSCLC): EORTC Lung Cancer Group 1613 APPLE phase II randomized clinical trial. Ann Oncol. 2023;34(5):468-76. https://doi.org/10.1016/j.annonc.2023.02.012
- Li S, Lai H, Liu J, Liu Y, Jin L, Li Y, et al. Circulating tumor DNA predicts the response and prognosis in patients with early breast cancer receiving neoadjuvant chemotherapy. JCO Precis Oncol. 2020;4:244-57. https://doi.org/10.1200/PO.19.00292
- Williams MJ, Vázquez-García I, Tam G, Wu M, Varice N, Havasov E, et al. Tracking clonal evolution during treatment in ovarian cancer using cell-free DNA. Nature. 2025;647(8090):757-65. doi:10.1038/s41586-025-09580-0
- Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016;8(346):346ra92. https://doi.org/10.1126/scitranslmed.aaf6219
- Tie J, Cohen JD, Lahouel K, Lo SN, Wang Y, Kosmider S, et al. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer. N Engl J Med. 2022;386(24):2261-72. https://doi.org/10.1056/NEJMoa2200075
- Moglia V, Johnson O, Cook G, de Kamps M, Smith L. Artificial intelligence methods applied to longitudinal data from electronic health records for prediction of cancer: a scoping review. BMC Med Res Methodol. 2025;25:24. https://doi.org/10.1186/s12874-025-02473-w
- Andaur Navarro CL, Damen JAA, Takada T, Nijman SWJ, Dhiman P, Ma J, et al. Risk of bias in studies on prediction models developed using supervised machine learning techniques: systematic review. BMJ. 2021;375:n2281. https://doi.org/10.1136/bmj.n2281
- Dhiman P, Ma J, Andaur Navarro CL, Speich B, Bullock G, Damen JAA, et al. Risk of bias of prognostic models developed using machine learning: a systematic review in oncology. Diagn Progn Res. 2022;6:13. https://doi.org/10.1186/s41512-022-00126-w
- Riley RD, Ensor J, Snell KIE, Harrell FE Jr, Martin GP, Reitsma JB, et al. Calculating the sample size required for developing a clinical prediction model. BMJ. 2020;368:m441. https://doi.org/10.1136/bmj.m441
- Van Calster B, McLernon DJ, van Smeden M, Wynants L, Steyerberg EW. Calibration: the Achilles heel of predictive analytics. BMC Med. 2019;17:230. https://doi.org/10.1186/s12916-019-1466-7
- Collins GS, Moons KGM, Dhiman P, Riley RD, Beam AL, Van Calster B, et al. TRIPOD+AI statement: updated guidance for reporting clinical prediction models that use regression or machine learning methods. BMJ. 2024;385:e078378. https://doi.org/10.1136/bmj-2023-078378
- Futoma J, Simons M, Panch T, Doshi-Velez F, Celi LA. The myth of generalisability in clinical research and machine learning in health care. Lancet Digit Health. 2020;2(9):e489-92. https://doi.org/10.1016/S2589-7500(20)30186-2
- Topol EJ. High-performance medicine: the convergence of human and artificial intelligence. Nat Med. 2019;25(1):44-56. doi:10.1038/s41591-018-0300-7
- Oluwadare OE, Frankpeace MS, Oluwaniran OM, Anatuanya JI, Onwuemelem LA. CRISPR Functional Genomics in Precision Oncology: Integrating Single-Cell Multi-Omics for Cancer Vulnerability Discovery. Oncology, Nuclear Medicine and Transplantology. 2026;2(3):onmt027. doi:10.63946/onmt/19194
- Oluwadare OE, Adeoba MI, Akor JT, Yusuff TA, Milimo P. The Rise of Smart Hospitals: Biomedical Engineering Innovations in Automation, Monitoring, and Digital Healthcare. Journal of Medicine and Health Research. 2026;11(2):121-38. doi:10.56557/jomahr/2026/v11i210794
- Malla M, Loree JM, Kasi PM, Parikh AR. Using circulating tumor DNA in colorectal cancer: current and evolving practices. J Clin Oncol. 2022;40(24):2846-57. doi:10.1200/JCO.21.02615
- Dasari A, Morris VK, Allegra CJ, Atreya C, Benson AB 3rd, Boland P, et al. ctDNA applications and integration in colorectal cancer: an NCI Colon and Rectal–Anal Task Forces whitepaper. Nat Rev Clin Oncol. 2020;17(12):757-70. doi:10.1038/s41571-020-0392-0
- Razavi P, Li BT, Brown DN, Jung B, Hubbell E, Shen R, et al. High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants. Nat Med. 2019;25(12):1928-37. doi:10.1038/s41591-019-0652-7
- Pantel K, Alix-Panabières C. Minimal residual disease as a target for liquid biopsy in patients with solid tumours. Nat Rev Clin Oncol. 2025;22:65-77. https://doi.org/10.1038/s41571-024-00967-y
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