Multidimensional Cellular Micro-Compartments to Model Invasive Lobular Carcinoma Dormancy

Sep 22, 2026

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Invasive lobular carcinoma (ILC) accounts for 10–15% of breast cancers, and despite favorable responses to anti-estrogen therapy, late recurrence and therapy resistance remain major clinical risks. Dormancy of disseminated tumor cells (DTCs) is proposed as a mechanism before overt metastatic growth. This study develops multidimensional, micro-compartmentalized in vitro models to examine the links between anti-estrogen resistance and dormancy.

LanguageEnglish

CategoryHealthcare

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Pages24

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Introduction

Clinical context of ILC dormancy

Limitations of current ILC models

Rationale for micro-compartmentalized in vitro platforms

Advanced Healthcare Materials [www.advhealthmat.de](www.advhealthmat.de) RESEARCH ARTICLE Multidimensional Cellular Micro-Compartments to Model Invasive Lobular Carcinoma Dormancy Xilal Y. Rima1, 2, 3 Sarmila Majumder3, 4 Divya S. Patel1 Chunyu Hu1 Hong Li1, 5 Xin Huang1 Kim Truc Nguyen1 Jacob Doon-Ralls1 Chiranth K. Nagaraj1 Mangesh D. Hade5 Setty M. Magaña5 Eswar Shankar3, 4 Xiaoli Zhang6 Daniel G. Stover3, 4 Bhuvaneswari Ramaswamy3, 4 Eduardo Reátegui1, 4 1William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio, USA 2 Diabetes and Metabolism Research Center, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA 3 Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA 4 Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA 5 Center for Clinical and Translational Research, Nationwide Children’s Hospital, Columbus, Ohio, USA 6 Department of Biomedical Informatics, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA Correspondence: Eduardo Reátegui ([reategui.8@osu.edu](reategui.8@osu.edu)) Received: 10 October 2025 Revised: 22 April 2026 Accepted: 11 May 2026 Keywords: cancer dormancy | invasive lobular carcinoma | microfluidics | micropatterning | photopolymerization ABSTRACT Invasive lobular carcinoma (ILC) accounts for 10–15% of breast cancers. Despite favorable responses to anti-estrogen therapy, the dissemination of cancer cells and resistance to therapies are significant risks for patients with ILC. Late recurrences are prevalent in ILC, suggesting that disseminated tumor cell (DTC) dormancy may be a mechanism preceding their late overt growth into metastatic lesions. Herein, we investigated the relationship between anti-estrogen resistance and dormancy through multidimensional, micro-compartmentalized in vitro models. The bioengineered platforms recapitulated the morphological characteristics of ILC and highlighted its distinction from invasive ductal carcinoma (IDC) . Inducing a reversible dormant phenotype revealed epigenetic changes and enhanced chemical and mechanical sensing of anti-estrogen-resistant ILC cells to the substrate surface, with p27Kip1 signaling playing a central role. We propose this platform as a high-throughput method for investigating ILC dormancy and its manifestation using a simplified, expedited approach. 1 Introduction The 5-year survival rate of localized breast cancers is >95%[1], attributed to advancements in loco-regional therapies, such as surgery and radiation [2], as well as effective systemic adjuvant therapies that target key molecular pathways [3, 4] . However, as breast cancer spreads to secondary sites, the 5-year survival rate reduces to ∼33%[1], indicating a critical role for disseminated tumor cells (DTCs) [5] . Recurrences can occur after long-term remission, serving as clinical evidence that DTCs acquire a dormant phenotype [6] and evade conventional therapeutic agents [7, 8] . Late recurrences are prevalent in hormone recep- tor (HR)-positive breast cancers [9] . Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two most common histologic subtypes of HR-positive breast cancer [10] . Despite comprising 10–15% of breast cancers, ILC is significantly understudied and clinically treated based on evidence from IDC research [11], notwithstanding its distinct morphological [12, 13], biomolecular [14, 15], and recurrence patterns [16–18] . Patients with ILC face lower rates of long-term disease-free and overall survival [19, 20], and have an increased number of circulating tumor cells (CTCs) or DTCs compared to patients with IDC [21, 22] . Although this suggests dormant DTCs may drive late recurrences in patients with ILC, studies on ILC dormancy are This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-

FAQs

Why is ILC dormancy considered important for late recurrences?

Late recurrences are common in ILC, and disseminated tumor cells (DTCs) may persist in a dormant state before later overt metastatic growth.

What kind of model platform is used to study ILC dormancy?

The study uses multidimensional, micro-compartmentalized bioengineered in vitro models to recreate key morphological features of ILC.

How does the model connect anti-estrogen resistance to dormancy?

By inducing a reversible dormant phenotype, the platform reveals epigenetic changes and increased chemical and mechanical sensing, with p27Kip1 signaling identified as central.

Sep 22, 2026

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