Signaling Pathways in Breast Cancer: 2nd Edition

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 15 December 2025 | Viewed by 1022

Special Issue Editor


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Guest Editor
Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010-3000, USA
Interests: carcinogenesis and metastases; chemoprevention; drug resistance; radiation resistance
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Special Issue Information

Dear Colleagues,

This Special Issue is the second edition of the Special Issue “Signaling Pathways in Breast Cancer”, available at: https://www.mdpi.com/journal/cancers/special_issues/Signaling_Pathways_Breast_Cancer

Breast cancer is a major cause of death among women in the Western world, who have a significant lifetime risk of developing the disease. Nearly 40,000 women succumb to breast cancer every year in the United States alone. Breast cancer is a heterogeneous disease broadly classified into subtypes, each with a distinct gene expression signature, including luminal-type, basal-like, human epidermal growth factor receptor 2-positive, and normal-like. Metastasis to multiple organs is the primary cause of mortality in breast cancer patients. HER2 is an important determinant of poor prognosis in breast cancer patients, and HER2-positive tumors are mostly resistant to therapy and have high metastatic potential. In addition, this Special Issue intends to provide a succinct overview of the availability and relevance of the major categories of mouse models for breast cancer. This Special Issue will concentrate on the latest achievements in developing genetically engineered mice (GEM) with conditional knockout alleles or models that allow the inducible expression of oncogenes in mammary epithelial cells.

Thus, this Special Issue aims to attract original research articles, clinical studies, and review articles describing the current findings on therapeutically promising natural products or small molecule inhibitors for future clinical use. We invite authors to submit articles exploring aspects of the therapeutic potential of natural products and/or small molecule inhibitor(s) in treating and suppressing breast cancer progression and metastasis.

Prof. Dr. Sharad S. Singhal
Guest Editor

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Keywords

  • angiogenesis
  • apoptosis
  • breast cancer metastasis
  • breast cancer stem cells
  • cancer invasion
  • chemoprevention
  • epithelial-to-mesenchymal transition
  • ERα/ERBB2/HER2/NFκB/Notch3/TGFβ signaling
  • mammary carcinogenesis
  • mitochondrial dynamics
  • tumor microenvironment

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Published Papers (1 paper)

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Research

12 pages, 2507 KiB  
Article
Targeting the Leukemia Inhibitory Factor/Leukemia Inhibitory Factor Receptor Axis Reduces the Growth of Inflammatory Breast Cancer by Promoting Ferroptosis
by Bianca Romo, Zenaida Fuentes, Lois Randolph, Megharani Mahajan, Emily J. Aller, Behnam Ebrahimi, Bindu Santhamma, Uday P. Pratap, Panneerdoss Subbarayalu, Harika Nagandla, Christoforos Thomas, Hareesh B. Nair, Ratna K. Vadlamudi and Suryavathi Viswanadhapalli
Cancers 2025, 17(5), 790; https://doi.org/10.3390/cancers17050790 - 25 Feb 2025
Viewed by 705
Abstract
Background: Inflammatory breast cancer (IBC) is a rare subtype of breast cancer accounting for 7% of breast cancer-related fatalities. There is an urgent need to develop new targeted treatments for IBC. The progression of IBC has been associated with alterations in growth factor [...] Read more.
Background: Inflammatory breast cancer (IBC) is a rare subtype of breast cancer accounting for 7% of breast cancer-related fatalities. There is an urgent need to develop new targeted treatments for IBC. The progression of IBC has been associated with alterations in growth factor and cytokine signaling; however, the function of the LIF (leukemia inhibitory factor)/LIFR (leukemia inhibitory factor receptor) cytokine pathway in the progression of IBC remains unknown. This study evaluated the role of LIFR signaling and tested the efficacy of the LIFR inhibitor EC359 in treating IBC. Methods: The utility of using LIFR inhibition as a treatment strategy in IBC was tested using cell survival, apoptosis, colony formation, invasion, and pre-clinical KPL4 xenografts. Western blotting, siRNA, RT-qPCR, and lipid peroxidation assays were used to establish the mechanism of EC359 therapy. Results: The reduction in LIFR levels using siRNA markedly decreased growth in colony formation assays and reduced the invasion of IBC cells. Pharmacological inhibition of LIFR with EC359 effectively reduced cell survival and the clonogenic capacity of IBC cells. RT-qPCR assays revealed that EC359 markedly decreased the expression of the LIFR target genes. Western blot analyses confirmed that EC359 treatment suppressed downstream LIF/LIFR signaling pathways and promoted apoptosis. Treatment of cells with the ferroptosis inhibitor Fer-1 negated the capacity of EC359 to induce apoptosis. Mechanistic investigations demonstrated that EC359 predominantly triggered ferroptosis by inhibiting the glutathione antioxidant defense system through the downregulation of Glutathione peroxidase 4 (GPX4) levels. EC359 (5 mg/kg/day) was effective in reducing the growth of the IBC KPL4 xenograft tumors. Conclusion: These findings demonstrates that LIFR inhibition promote ferroptosis-mediated cell death in IBC and that EC359 represent novel therapeutic for IBC treatment. Full article
(This article belongs to the Special Issue Signaling Pathways in Breast Cancer: 2nd Edition)
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