Dysregulated Signaling Pathways in Canine Mammary Tumor and Human Triple Negative Breast Cancer: Advances and Potential Therapeutic Targets

Overview

Journal Int J Mol Sci

Publisher MDPI

Date 2025 Jan 11

PMID 39796003

Authors

Chen Mei

Ying Liu

Zhenyi Liu

Yan Zhi

Zhaoling Jiang

Xueze Lyu

Hongjun Wang

Affiliations

Soon will be listed here.

Abstract

In 2022, human breast cancer (HBC) and canine mammary tumors (CMTs) remained the most prevalent malignant tumors worldwide, with high recurrence and lethality rates, posing a significant threat to human and dog health. The development of breast cancer involves multiple signaling pathways, highlighting the need for effective inhibitory drugs that target key proteins in these pathways. This article reviews the dysregulation of the EGFR, PI3K/AKT/mTOR, Hippo, pyroptosis, and PD-1/PD-L1 signaling pathways in HBC and CMT, as well as the corresponding drugs used to inhibit tumor growth, with the aim of providing theoretical support for the development of more efficient drugs.

References

Tang J, Bei M, Zhu J, Xu G, Chen D, Jin X . Acute cadmium exposure induces GSDME-mediated pyroptosis in triple-negative breast cancer cells through ROS generation and NLRP3 inflammasome pathway activation. Environ Toxicol Pharmacol. 2021; 87:103686. DOI: 10.1016/j.etap.2021.103686. View

Wang S, Chang C, Huang J, Zeng S, Zhang X, Hung M . Gasdermin C sensitizes tumor cells to PARP inhibitor therapy in cancer models. J Clin Invest. 2023; 134(1). PMC: 10760963. DOI: 10.1172/JCI166841. View

Varney D, ONeill D, ONeill M, Church D, Stell A, Beck S . Epidemiology of mammary tumours in bitches under veterinary care in the UK in 2016. Vet Rec. 2023; 193(5):e3054. DOI: 10.1002/vetr.3054. View

Miles D, Gligorov J, Andre F, Cameron D, Schneeweiss A, Barrios C . Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol. 2021; 32(8):994-1004. DOI: 10.1016/j.annonc.2021.05.801. View

Yan H, Luo B, Wu X, Guan F, Yu X, Zhao L . Cisplatin Induces Pyroptosis via Activation of MEG3/NLRP3/caspase-1/GSDMD Pathway in Triple-Negative Breast Cancer. Int J Biol Sci. 2021; 17(10):2606-2621. PMC: 8315016. DOI: 10.7150/ijbs.60292. View

Fenn K, Maurer M, Lee S, Crew K, Trivedi M, Accordino M . Phase 1 Study of Erlotinib and Metformin in Metastatic Triple-Negative Breast Cancer. Clin Breast Cancer. 2019; 20(1):80-86. PMC: 7304226. DOI: 10.1016/j.clbc.2019.08.004. View

Cordeiro Y, Mulder L, van Zeijl R, Paskoski L, van Veelen P, de Ru A . Proteomic Analysis Identifies FNDC1, A1BG, and Antigen Processing Proteins Associated with Tumor Heterogeneity and Malignancy in a Canine Model of Breast Cancer. Cancers (Basel). 2021; 13(23). PMC: 8657005. DOI: 10.3390/cancers13235901. View

Lee J, Kim J, Jeong D, Kim M . Transcriptional activation of EGFR by HOXB5 and its role in breast cancer cell invasion. Biochem Biophys Res Commun. 2018; 503(4):2924-2930. DOI: 10.1016/j.bbrc.2018.08.071. View

An H, Heo J, Kim P, Lian Z, Lee S, Park J . Tetraarsenic hexoxide enhances generation of mitochondrial ROS to promote pyroptosis by inducing the activation of caspase-3/GSDME in triple-negative breast cancer cells. Cell Death Dis. 2021; 12(2):159. PMC: 7870965. DOI: 10.1038/s41419-021-03454-9. View

10.

Hurvitz S, Hegg R, Chung W, Im S, Jacot W, Ganju V . Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2022; 401(10371):105-117. DOI: 10.1016/S0140-6736(22)02420-5. View

11.

Huang D, Zou Y, Huang H, Yin J, Long S, Sun W . A PROTAC Augmenter for Photo-Driven Pyroptosis in Breast Cancer. Adv Mater. 2024; 36(21):e2313460. DOI: 10.1002/adma.202313460. View

12.

Salas Y, Marquez A, Diaz D, Romero L . Epidemiological Study of Mammary Tumors in Female Dogs Diagnosed during the Period 2002-2012: A Growing Animal Health Problem. PLoS One. 2015; 10(5):e0127381. PMC: 4436381. DOI: 10.1371/journal.pone.0127381. View

13.

Xing Y, Zhang F, Ji P, Wei M, Yin C, Yang A . Efficient Delivery of GSDMD-N mRNA by Engineered Extracellular Vesicles Induces Pyroptosis for Enhanced Immunotherapy. Small. 2023; 19(20):e2204031. DOI: 10.1002/smll.202204031. View

14.

Cui N, Qiao S, Jiang S, Hu J, Wang T, Liu W . Protein Tyrosine Kinase 7 Regulates EGFR/Akt Signaling Pathway and Correlates With Malignant Progression in Triple-Negative Breast Cancer. Front Oncol. 2021; 11:699889. PMC: 8339706. DOI: 10.3389/fonc.2021.699889. View

15.

Drago J, Ferraro E, Abuhadra N, Modi S . Beyond HER2: Targeting the ErbB receptor family in breast cancer. Cancer Treat Rev. 2022; 109:102436. PMC: 10478787. DOI: 10.1016/j.ctrv.2022.102436. View

16.

Zeng B, Pian L, Liu Y, Wang S, Wang N, Liu C . Preparation and effects of functionalized liposomes targeting breast cancer tumors using chemotherapy, phototherapy, and immunotherapy. J Nanobiotechnology. 2024; 22(1):558. PMC: 11391708. DOI: 10.1186/s12951-024-02838-1. View

17.

Monteleone M, Stanley A, Chen K, Brown D, Bezbradica J, von Pein J . Interleukin-1β Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion. Cell Rep. 2018; 24(6):1425-1433. DOI: 10.1016/j.celrep.2018.07.027. View

18.

Loi S, Michiels S, Salgado R, Sirtaine N, Jose V, Fumagalli D . Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol. 2014; 25(8):1544-50. DOI: 10.1093/annonc/mdu112. View

19.

Zak K, Grudnik P, Magiera K, Domling A, Dubin G, Holak T . Structural Biology of the Immune Checkpoint Receptor PD-1 and Its Ligands PD-L1/PD-L2. Structure. 2017; 25(8):1163-1174. DOI: 10.1016/j.str.2017.06.011. View

20.

Wollman A, Fournier C, Llorente-Garcia I, Harriman O, Payne-Dwyer A, Shashkova S . Critical roles for EGFR and EGFR-HER2 clusters in EGF binding of SW620 human carcinoma cells. J R Soc Interface. 2022; 19(190):20220088. PMC: 9131850. DOI: 10.1098/rsif.2022.0088. View