A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer

Sep 24, 2026

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Triple-negative breast cancer (TNBC) is a heterogeneous, aggressive breast cancer subtype linked to chemoresistance and poor prognosis. Chemo- or radioresistance is associated with diverse tumor microenvironments, membrane protein overexpression (including transporters), epigenetic alterations, and disrupted cell signaling programs that promote cancer stem cells (CSCs). The review synthesizes key contributory factors and highlights blockade strategies of multiple pathways and receptors, alongside therapeutic modalities aimed at reversing chemoresistance and limiting TNBC progression.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages22

Reading Time55 min

AccessFree to download

Highlights

Chemoresistance mechanisms in TNBC

Tumor microenvironment and transporter overexpression

Cell signaling pathways and cancer stem cells

Targeted blockade of pathways and receptors

Therapeutic modalities and reversal of chemoresistance

Journal of Advanced Research 54 (2023) 271–292 Contents lists available at ScienceDirect Journal of Advanced Research journal [homepage: www. elsevier. com/locate/jare](homepage: www. elsevier. com/locate/jare) A review of biological targets and therapeutic approaches in the management of triple-negative breast cancer Hitesh Kumar a, N. Vishal Gupta a, Rupshee Jain b, SubbaRao V. Madhunapantula c, C. Saravana Babud, Siddharth S. Kesharwani e, Surajit Dey f, Vikas Jain a, ⇑ a Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, India b Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, India c Department of Biochemistry, Centre of Excellence in Molecular Biology & Regenerative Medicine, JSS Medical College, JSS Academy of Higher Education & Research, Mysuru 570015, India d Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru 570015, India e Roseman University of Health Sciences, College of Pharmacy, South Jordan, UT, USA f Roseman University of Health Sciences, College of Pharmacy, Henderson, NV, USA h i g h l i g h t s 􀀁 This review addresses the major contributory factors responsible for chemoresistance and poor prognosis in TNBC. 􀀁 Diverse TME, overexpression of transporters, genetic and epigenetic changes play a crucial role. 􀀁 Alteration of the cell signaling pathways and cancer stem cells (CSCs) help in chemoresistance development. 􀀁 Blockade of multiple cell signaling pathways and receptors are potential to inhibit TNBC progression. 􀀁 Therapeutic modalities including reversal of chemoresistance are broadly discussed. g r a p h i c a l a b s t r a c t Abbreviations: AKT, Ak strain transforming; ALDH, aldehyde dehydrogenase; AR, Androgen receptor; ABC, ATP-binding cassette; ABCB5, ATP-binding cassette member B5; BL1, Basal-like1; BL2, Basal-like 2; BC, Breast cancer; BRCP, breast cancer resistance protein; CAAs, Cancer-associated adipocytes; CAFs, Cancer-associated ﬁbroblasts; CSCs, cancer stem cells; CNTs, Carbon nanotubes; JNK, c-Jun N-terminal kinase; pCR, complete pathologic response; CD, Cluster of diffraction; DTX, docetaxel, DOX, doxorubicin; DMT, DNA methyltransferasem; EPR, enhanced permeability and retention; EGFR, endothelial growth receptor factor; EMT, epithelial-to-mesenchymal transition; ER, estrogen receptors; ECM, extracellular matrix; FGFR, Fibroblast growth factor receptor; FA, folic acid; FR, Folate receptor; GLUT, glucose transporters; GNPs, Gold nanoparticles; Hh, hedgehog; HOla, H-ferritin nanocage; HAT, histone acetyl transferase; HDAC, histone deacetylase; HMT, histone methyl transferase; HER-2, human epidermal growth factor-2; HA, Hyaluronic acid; HIF-1a, hypoxia-inducible factor-1a; IM, immune modulatory; ICAM-1, intercellular adhesion molecule-1; LAR, luminalandrogen receptor; mTOR, mammalian target of rapamycin; MASCs, mammary stem cells; MTX, methotrexate; MSL, mesenchymal stem-like; miRNA, microRNA; mAbs, monoclonal antibody; MDR, multidrug resistance; MRP-1, multidrug resistance protein-1; NPs, nanoparticles; nRTKs, nonreceptor tyrosine kinases; LbL, layer by layer; OXPHOS, oxidative phosphorylation; PTX, paclitaxel; P-gp 1, P-glycoprotein 1; PI3K, Phosphoinositide 3-kinase; PIP2, phosphatidylinositol (3,4)P2; PIP3, phosphatidylinositol (3,4,5)P3; PDT, photodynamic therapy; PDGF, platelet-derived growth factor; MEH-PPV, poly[2-methoxy-5-(2-ethyl-hexyloxy)-1,4-phenylenevinylene]; PAMAM, polyamidoamine; PEG, polyethylene glycols; PARP, Poly ADP-ribose, Polymerase; PARPi, poly ADP-ribose polymerase Enzymes inhibitors; PLA, poly lactic acid; PLGA, poly lactic-coglycolic acid; PR, progesterone receptors; PD-1, programmed cell death-1; PD-L1, programmed cell death-1 ligand; QDs, quantum dots; ROS, reactive oxygen species; RTKs, receptor tyrosine kinases; SMO, smoothened; SOX2, SR

FAQs

What is the central focus of the review on triple-negative breast cancer?

The review summarizes major biological factors driving chemoresistance and poor prognosis in TNBC, and discusses therapeutic approaches that target these mechanisms.

Which tumor-related factors contribute to chemoresistance and poor prognosis in TNBC?

Key factors include diverse tumor microenvironments, overexpression of membrane transporters, genetic and epigenetic changes, and alterations in cell signaling that support cancer stem cell development.

How does the review propose therapeutic strategies to inhibit TNBC progression?

It emphasizes blocking multiple cell signaling pathways and receptors and discusses therapeutic modalities aimed at reversing chemoresistance in TNBC.

Sep 24, 2026

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