Advancements in Single-Cell Proteomics and Mass Spectrometry-Based Techniques for Unmasking Cellular Diversity in Triple Negative Breast Cancer - Review

Sep 21, 2026

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Triple-negative breast cancer (TNBC) is an aggressive, complex subtype lacking effective targeted therapies. Intratumoral heterogeneity drives disease progression and undermines therapeutic responses, requiring advanced analytical tools to clarify underlying biology. This review evaluates how single-cell proteomics and mass spectrometry-based methods can reveal cellular diversity in TNBC, emphasizing innovations in sample preparation, proteomic protein-analysis challenges, and integration of proteomics into multi-omics platforms. Single-cell proteomics links phenotype and cell behavior and complements transcriptomics.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Introduction

Triple-negative breast cancer background and clinical challenge

Single-cell proteomics and mass spectrometry-based approaches

Sample preparation innovations

Mass spectrometry techniques and data interpretation

Integration into multi-omics platforms

Challenges and protein-analysis limitations

Results and implications

Conclusion

PROTEOMICS – Clinical Applications REVIEW Advancements in Single-Cell Proteomics and Mass Spectrometry-Based Techniques for Unmasking Cellular Diversity in Triple Negative Breast Cancer Lakshmi Vineela Nalla1 Aarika Kanukolanu2 Madhuri Yeduvaka1 Siva Nageswara Rao Gajula2 1 Department of Pharmacology, GITAM School of Pharmacy, GITAM (Deemed to be University), Visakhapatnam, Andhra Pradesh, India 2 Department of Pharmaceutical Analysis, GITAM School of Pharmacy, GITAM (Deemed to be University), Visakhapatnam, Andhra Pradesh, India Correspondence: Siva Nageswara Rao Gajula ([sgajula@gitam.edu](sgajula@gitam.edu); [sivapharma.93@gmail.com](sivapharma.93@gmail.com)) Received: 11 October 2024 Revised: 4 November 2024 Accepted: 8 November 2024 Funding: The authors received no specific funding for this work. Keywords: intratumoral heterogeneity | mass spectrometry | multi-omics platform | single-cell proteomics | triple-negative breast cancer ABSTRACT Background: Triple-negative breast cancer (TNBC) is an aggressive and complex subtype of breast cancer characterized by a lack of targeted treatment options. Intratumoral heterogeneity significantly drives disease progression and complicates therapeutic responses, necessitating advanced analytical approaches to understand its underlying biology. This review aims to explore the advancements in single-cell proteomics and their application in uncovering cellular diversity inTNBC. It highlights innovations in sample preparation, mass spectrometry-based techniques, and the potential for integrating proteomics into multi-omics platforms. Methods: The review discusses the combination of improved sample preparation methods and cutting-edge mass spectrometry techniques in single-cell proteomics. It emphasizes the challenges associated with protein analysis, such as the inability to amplify proteins akin to transcripts, and examines strategies to overcome these limitations. Results: Single-cell proteomics provides a direct link to phenotype and cell behavior, complementing transcriptomic approaches and offering new insights into the mechanisms driving TNBC. The integration of advanced techniques has enabled deeper exploration of cellular heterogeneity and disease mechanisms. Conclusion: Despite the challenges, single-cell proteomics holds immense potential to evolve into a high-throughput and scalable multi-omics platform. Addressing existing hurdles will enable deeper biological insights, ultimately enhancing the diagnosis and treatment ofTNBC. 1 Introduction Breast cancer (BC) is a heterogeneous disease whose clinical subtypes vary in molecular characteristics, prognosis, and therapeutic responsiveness [1–3] . Genomic research has directed toa more distinct classification of BCs based on their genes and proteins. For hormone receptor-positive cancer, where estrogen (ER-positive) and progesterone (PR-positive) fuel cancer’s growth, have BC cells with receptors [4] . In contrast, hormone receptor-negative BC cells lack receptors. These receptor-negative cancers are unhelpful from hormone therapy drugs and tend to grow faster than hormone receptor-positive cancers. BC cells that rely on human epidermal growth factor receptor 2 (HER2) for growth are HER2-positive, and less dependent are HER2-negative [5, 6] . In triple-negative BC, all three protein expression systems are absent [7]. The risk of developing BC increases in women with a BC in family history, lifestyle, diet, and the environment [8] . Heredity-based BC is due to the mutations in abnormal breast This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2024 The Author(s). PROTEOMICS-Clinical Applications published by Wiley-VCH GmbH. PROTEOMICS – Clinical Applications,

FAQs

Why is intratumoral heterogeneity important in triple-negative breast cancer (TNBC)?

Intratumoral heterogeneity drives TNBC disease progression and complicates therapeutic responses, making it essential to study the underlying biology with advanced analytical methods.

What is the focus of this review?

The review focuses on advancements in single-cell proteomics and mass spectrometry-based techniques to uncover cellular diversity in TNBC, including sample preparation innovations and the integration of proteomics into multi-omics platforms.

How does single-cell proteomics contribute compared with transcriptomics?

Single-cell proteomics provides a direct link to phenotype and cell behavior, complementing transcriptomic approaches and offering insights into mechanisms driving TNBC cellular heterogeneity.

Sep 21, 2026

Uploaded by Aurelia