Triple-Negative Breast Cancer: Basic Biology and Immuno-Oncolytic Viruses

Sep 24, 2026

Uploaded by Aria

Triple-negative breast cancer (TNBC) is the most lethal breast cancer subtype, comprising about one-fifth of global cases. Its lack of estrogen, progesterone, and HER-2 receptors prevents established molecular targeted options, leaving chemotherapy and surgery as common standards and increasing treatment difficulty. High recurrence rates, tumor heterogeneity, and differing mutational burdens further hinder durable control. This review outlines six TNBC gene-expression-defined subtypes, explains how subtype differences influence metastasis and resistance, and summarizes emerging immuno-oncolytic virus strategies designed to enhance antitumor immune effects.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages25

Reading Time1 h 3 min

AccessFree to download

Introduction

Triple-Negative Breast Cancer (TNBC)

Simple Summary

Abstract

Keywords

Biology and Subtypes of TNBC

Immuno-oncolytic Virus Strategies

cancers Review Triple-Negative Breast Cancer: Basic Biology and Immuno-Oncolytic Viruses Michael L. Monaco, Omer A. Idris and Karim Essani * Citation: Monaco, M.L.; Idris, O.A.; Essani, K. Triple-Negative Breast Cancer: Basic Biology and Immuno-Oncolytic Viruses. Cancers 2023, 15, 2393. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/cancers15082393](10.3390/cancers15082393) Academic Editors: Wei Wei, V²steinn Thârsson and Yin Tang Received: 30 March 2023 Revised: 13 April 2023 Accepted: 19 April 2023 Published: 21 April 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . Laboratory of Virology, Department of Biological Sciences, Western Michigan University, Kalamazoo, MI 49008, USA; [michael.l.monaco@wmich.edu](michael.l.monaco@wmich.edu) (M.L.M.); [omer.a.idris@wmich.edu](omer.a.idris@wmich.edu) (O.A.I.) * Correspondence: [karim.essani@wmich.edu](karim.essani@wmich.edu); Tel.: +1-269-387-2661 Simple Summary: Triple-negative breast cancer (TNBC) is an aggressive as well as the most dangerous form of breast cancer. Due to the lack of biomarkers that can be targeted by speciﬁc molecular therapeutics, treatment is usually limited to chemotherapy and surgery where applicable. Oncolytic viruses are biologicals that have been engineered in many cases to express different genes that can aid in the recruitment of immune cells to trigger antitumor immune responses in addition to the direct lysis of infected cancerous cells. In this review, the basic biology of TNBC is described, as are the many OVs and their different strategies to attempt to treat TNBC in vitro, in vivo, and inhuman trials. Abstract: Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. TNBC diagnoses account for approximately one-ﬁfth of all breast cancer cases globally. The lack of receptors for estrogen, progesterone, and human epidermal growth factor 2 (HER-2, CD340) results in a lack of available molecular-based therapeutics. This increases the difﬁculty of treatment and leaves more traditional as well as toxic therapies as the only available standards of care in many cases. Recurrence is an additional serious problem, contributing substantially to its higher mortality rate as compared to other breast cancers. Tumor heterogeneity also poses a large obstacle to treatment approaches. No driver of tumor development has been identiﬁed for TNBC, and large variations in mutational burden between tumors have been described previously. Here, we describe the biology of six different subtypes of TNBC, based on differential gene expression. Subtype differences can have a large impact on metastatic potential and resistance to treatment. Emerging antibody-based therapeutics, such as immune checkpoint inhibitors, have available targets for small subsets of TNBC patients, leading to partial responses and relatively low overall efﬁcacy. Immuno-oncolytic viruses (OVs) have recently become signiﬁcant in the pursuit of effective treatments for TNBC. OVs generally share the ability to ignore the heterogeneous nature of TNBC cells and allow infection throughout a treated tumor. Recent genetic engineering has allowed for the enhancement of efﬁcacy against certain tumor types while avoiding the most common side effects in non-cancerous tissues. In this review, TNBC is described in order to address the challenges it presents to potential treatments. The OVs currently described preclinically and in various stages of clinical trials are also summarized, as are their strategies to enhance therapeutic potential. Keywords: triple-negative breast cancer; immuno-oncolytic viruses; cancer biology; virotherapy

FAQs

Why is TNBC considered difficult to treat compared with other breast cancer subtypes?

TNBC lacks receptors for estrogen, progesterone, and HER-2, which removes many molecular targeted therapeutic options. This typically forces reliance on more traditional and often toxic treatments such as chemotherapy and surgery where applicable.

How are TNBC subtypes described in the review?

The review describes six TNBC subtypes based on differential gene expression. These include basal-like (BL1/BL2), mesenchymal (M), mesenchymal-stem-cell-like (MSL), immunomodulatory (IM), and luminal androgen receptor (LAR).

What role do immuno-oncolytic viruses (OVs) play in TNBC treatment approaches?

Immuno-oncolytic viruses are engineered agents intended to support antitumor immune responses. They aim to promote infection throughout tumors, enhance efficacy for certain tumor types, and help trigger immune-mediated responses beyond direct lysis of infected cancer cells.

Sep 24, 2026

Uploaded by Aria