Identifying Therapeutic Targets for Triple-Negative Breast Cancer using a Novel Mathematical Model of the Tumor Microenvironment

Fuente: arXiv
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Auteurs principaux: Adams, Kyle, Bruner, Julia, Ameziane, Salma, Brown, Ashley, Gbadamosi, Mohammed, Moore, Helen
Format: Preprint
Publié: 2026
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author Adams, Kyle
Bruner, Julia
Ameziane, Salma
Brown, Ashley
Gbadamosi, Mohammed
Moore, Helen
author_facet Adams, Kyle
Bruner, Julia
Ameziane, Salma
Brown, Ashley
Gbadamosi, Mohammed
Moore, Helen
contents Triple-negative breast cancer (TNBC) is an aggressive disease with high mortality and limited treatment options, due to its lack of receptors that have targeted therapies available. The tumor microenvironment (TME) plays a critical role in TNBC progression and therapeutic resistance. In this work, we developed a novel mathematical model to describe key cellular interactions within the TNBC TME, informed by current literature and expert input. Our model consists of a system of ordinary differential equations representing five interacting cell populations: M2 macrophages, cancer-associated fibroblasts, TNBC tumor cells, cytotoxic T lymphocytes, and regulatory T cells. We performed global sensitivity analysis to determine which model parameters most strongly influence tumor burden over a clinically-relevant treatment timeframe. The pathways associated with the most-influential parameters correspond to biological mechanisms that are consistent with known and emerging therapeutic strategies in TNBC, including stromal-mediated tumor support. These results highlight key regulatory interactions within the TNBC TME and provide a quantitative framework for hypothesis generation and future investigation of combination treatment strategies.
format Preprint
id arxiv_https___arxiv_org_abs_2601_12455
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle Identifying Therapeutic Targets for Triple-Negative Breast Cancer using a Novel Mathematical Model of the Tumor Microenvironment
Adams, Kyle
Bruner, Julia
Ameziane, Salma
Brown, Ashley
Gbadamosi, Mohammed
Moore, Helen
Quantitative Methods
Triple-negative breast cancer (TNBC) is an aggressive disease with high mortality and limited treatment options, due to its lack of receptors that have targeted therapies available. The tumor microenvironment (TME) plays a critical role in TNBC progression and therapeutic resistance. In this work, we developed a novel mathematical model to describe key cellular interactions within the TNBC TME, informed by current literature and expert input. Our model consists of a system of ordinary differential equations representing five interacting cell populations: M2 macrophages, cancer-associated fibroblasts, TNBC tumor cells, cytotoxic T lymphocytes, and regulatory T cells. We performed global sensitivity analysis to determine which model parameters most strongly influence tumor burden over a clinically-relevant treatment timeframe. The pathways associated with the most-influential parameters correspond to biological mechanisms that are consistent with known and emerging therapeutic strategies in TNBC, including stromal-mediated tumor support. These results highlight key regulatory interactions within the TNBC TME and provide a quantitative framework for hypothesis generation and future investigation of combination treatment strategies.
title Identifying Therapeutic Targets for Triple-Negative Breast Cancer using a Novel Mathematical Model of the Tumor Microenvironment
topic Quantitative Methods
url https://arxiv.org/abs/2601.12455