Cancer treatment by radioimmunotherapy: insights from a dynamical model of cancer stem cells and hypoxia effects

Sep 22, 2026

Cancer treatment by radioimmunotherapy is analyzed through an approach combining analytical and computational dynamical modeling of cancer stem cells and hypoxia effects. The study incorporates time-delay dynamics and interactions between microRNAs and differentiated cancer cells, and uses extrapolated dose rates from key radionuclides (90Y, 177Lu, 131I, 225Ac) to assess preventive efficacy before recurrence. Linear-quadratic formalism enables comparison via biological effective dose, surviving fraction, and tumor control probability, while sensitivity analysis tests robustness. Results show strong CSC and differentiated-cell eradication with 225Ac and 177Lu near 165 Gy·year−1, and improved CSC radiosensitivity under enhanced oxygen availability.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages22

Reading Time55 min

AccessFree to download

Abstract

Modeling framework

Radionuclide dose evaluation

Sensitivity analysis and robustness

Dose-threshold and microRNA effects

Hypoxia and oxygenation impact

Protocol optimization implications

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Cancer treatment by radioimmunotherapy: insights from a dynamical model of cancer stem cells and hypoxia effects Alain Mvogo1􀀍, Frank Eric Essongo2 & Germain Hubert Ben-Bolie2 Cancer remains a major challenge for conventional treatments. This is due to the resistance mechanisms driven by cancer stem cells (CSCs) which sustain tumor growth. In this work, we investigate both analytically and computationally the effects of radioimmunotherapy (RIT), a cuttingedge technique that uses radiolabeled antibodies to precisely target and irradiate cancer cells. The work considers time delay modeling and the interactions between microRNAs and differentiated cancer cells (DCs). We evaluate the effects of extrapolated dose rates from four important radionuclides including yttrium-90 (90Y), lutetium-177 (177 Lu), iodine-131 (131 I) and actinium-225 (225 Ac) in the preventive treatment of cancer before recurrence. A sensitivity analysis of model parameters is also performed to assess the robustness of the predictions and to identify the most influential biological and physical variables. Using the linear-quadratic formalism, we compare their biological effective dose, surviving fraction, and tumor control probability. The results demonstrate that an extrapolated initial dose of 165 Gy.year−1 leads to an eradication of CSCs using 225 Ac and 177 Lu within 1.4636 year and 1.5736 year, respectively. Similarly, DCs are eliminated with 225 Ac and 177 Lu over treatment durations of 0.9396 year and 1.0496 year, respectively. These results highlight the potent effects of 225 Ac and 177 Lu in targeting CSCs and DCs at this dose rate. Under these conditions, microRNAs act as tumor suppressors, thus preventing pro-tumorigenic effects. Exceeding the dose threshold (beyond 165 Gy.year−1) disrupts the therapeutic balance with an efficacy which decreases progressively. For the doses above 326 Gy.year−1, the overproliferation of CSCs and DCs is observed with an oncogenic behavior of microRNAs. We further examine the role of tumor oxygenation in modulating RIT efficacy. The results reveal that enhancing oxygen availability significantly increases CSC radiosensitivity, which is otherwise reduced under hypoxic conditions. The results of this work provide insight in optimizing RIT protocols using radiolabeled agents with improved pharmacokinetics and biological half-lives. Keywords Cancer model, Radioimmunotherapy, Biological effective clearance half-life, Tumor control probability, Hypoxia, Circular patterns Cancer represents a challenge in modern medicine, marked by its complex and heterogeneous nature, leading to significant morbidity and mortality worldwide1. Cancer stem cells (CSCs) are a subclass of cancer cells that can differentiate into various cell types and self-renew, similar to normal stem cells2. Recent investigations have shown that CSCs play a central role in the initiation, progression and resistance to cancer treatments. Unlike differentiated cancer cells (DCs), CSCs possess self-renewal and differentiation capabilities, which promote tumor heterogeneity and contribute to relapses3–7. Their plasticity allows them to adapt to the tumor microenvironment, while their resistance to conventional therapies, such as chemotherapy and radiotherapy, complicates the complete eradication of tumors. Due to these characteristics, CSCs have become major targets for the development of novel therapeutic strategies aimed at enhancing treatment efficacy and minimizing relapse8–10. The clinical relevance of targeting CSCs in radioimmunotherapy (RIT) lies in their resistance to standard therapies, making them key contributors to cancer recurrence and metastasis. RIT is a targeted cancer treatment 1Laboratory of Biophysics, Department of Physics, Faculty of Science, University of Yaounde I, P.O. Box 812, Yaounde, Cameroon. 2Laboratory of Nuclear Physics, Dosimetry and Radiation

FAQs

What biological and mathematical factors are included in the radioimmunotherapy model?

The model includes time-delay dynamics and interactions between microRNAs and differentiated cancer cells, while representing cancer stem cells as a driver of resistance and tumor persistence.

How are different radionuclides evaluated in the study?

Extrapolated dose rates from 90Y, 177Lu, 131I, and 225Ac are assessed using linear-quadratic formalism, comparing biological effective dose, surviving fraction, and tumor control probability.

What does the study indicate about the dose threshold and microRNA behavior?

An initial dose around 165 Gy·year−1 can eradicate cancer stem cells and differentiated cells with 225Ac and 177Lu, while doses beyond 165 Gy·year−1 progressively reduce efficacy and above 326 Gy·year−1 lead to oncogenic microRNA behavior with excessive proliferation.

How does oxygenation influence radioimmunotherapy efficacy under hypoxic conditions?

Increasing oxygen availability significantly increases cancer stem cell radiosensitivity, which is otherwise reduced under hypoxia, thereby modulating overall RIT efficacy.

Sep 22, 2026

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