Phenotypic maps for precision medicine: a promising systems biology tool for assessing therapy response and resistance at a personalized level

Sep 28, 2026

Perspective examining how tumor heterogeneity and therapy resistance drive the need for more personalized approaches in precision medicine. The article positions omics-driven systems biology and high-throughput technologies to build systems-based phenotypic maps that reveal individual tumor functional plasticity. It spotlights PHENOSTAMP, a high-dimensional, visually intuitive reference map capturing transitional cancer states such as EMT and MET and enabling assessment of therapy response and resistance at single-cell resolution.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Introduction

Limits of marker-based personalization

Heterogeneity, TME interactions, and resistance

PHENOSTAMP and phenotypic maps

Single-cell EMT/MET state visualization

Reference mapping for clinical specimens

Outlook for precision oncology

TYPE Perspective PUBLISHED 25 October 2023 DOI 10.3389/fnetp.2023.1256104 OPEN ACCESS EDITED BY Mohit Kumar Jolly, Indian Institute of Science (IISc), India REVIEWED BY Sugandha Bhatia, Queensland University of Technology, Australia Nandini Verma, Advanced Centre for Treatment, Research and Education in Cancer, India *CORRESPONDENCE Loukia G. Karacosta, [lgkaracosta@mdanderson.org](lgkaracosta@mdanderson.org) †These authors have contributed equally to this work and share ﬁrst authorship RECEIVED 10 July 2023 ACCEPTED 28 September 2023 PUBLISHED 25 October 2023 CITATION Bhattacharyya S, Ehsan SF and Karacosta LG (2023), Phenotypic maps for precision medicine: a promising systems biology tool for assessing therapy response and resistance at a personalized level. Front. Netw. Physiol. 3:1256104 . doi: 10.3389/fnetp.2023.1256104 COPYRIGHT © 2023 Bhattacharyya, Ehsan and Karacosta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Phenotypic maps for precision medicine: a promising systems biology tool for assessing therapy response and resistance at a personalized level Sayantan Bhattacharyya 1†, Shafqat F. Ehsan 1,2† and Loukia G. Karacosta 1* 1Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, United States, 2Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States In this perspective we discuss how tumor heterogeneity and therapy resistance necessitate a focus on more personalized approaches, prompting a shift toward precision medicine. At the heart of the shift towards personalized medicine, omics-driven systems biology becomes a driving force as it leverages highthroughput technologies and novel bioinformatics tools. These enable the creation of systems-based maps, providing a comprehensive view of individual tumor’s functional plasticity. We highlight the innovative PHENOSTAMP program, which leverages high-dimensional data to construct a visually intuitive and userfriendly map. This map was created to encapsulate complex transitional states in cancer cells, such as Epithelial-Mesenchymal Transition (EMT) and MesenchymalEpithelial Transition (MET), offering a visually intuitive way to understand disease progression and therapeutic responses at single-cell resolution in relation to EMTrelated single-cell phenotypes. Most importantly, PHENOSTAMP functions as a reference map, which allows researchers and clinicians to assess one clinical specimen at a time in relation to their phenotypic heterogeneity, setting the foundation on constructing phenotypic maps for personalized medicine. This perspective argues that such dynamic predictive maps could also catalyze the development of personalized cancer treatment. They hold the potential to transform our understanding of cancer biology, providing a foundation for a future where therapy is tailored to each patient’s unique molecular and cellular tumor proﬁle. As our knowledge of cancer expands, these maps can be continually reﬁned, ensuring they remain a valuable tool in precision oncology. KEYWORDS personalized medicine, phenotypic maps, therapy resistance, tumor heterogeneity, multi-omics, systems biology, computational biology Introduction Therapy resistance remains the major culprit of cancer related mortality (Vasan et al., 2019). Overcoming resistance poses a signiﬁcant challenge given the intra-and inter-heterogeneity of tumors and the plastic nature of therapy resistant phenotypes that develop over time during treatment (Zhu

FAQs

Why does therapy resistance require personalized approaches in precision medicine?

Therapy resistance is driven by tumor intra- and inter-heterogeneity plus the plasticity of resistant phenotypes that evolve during treatment. These factors make uniform strategies insufficient for durable responses.

How does systems biology support the shift toward personalized medicine?

Omics-driven systems biology uses high-throughput technologies and novel bioinformatics tools to construct systems-based maps. These maps provide a comprehensive view of individual tumors’ functional plasticity.

What is PHENOSTAMP and what does its phenotypic map enable?

PHENOSTAMP builds a visually intuitive, user-friendly reference map from high-dimensional data. It captures transitional states such as EMT and MET and helps researchers and clinicians assess a clinical specimen one at a time relative to phenotypic heterogeneity.

Sep 28, 2026

Uploaded by 4398046744996