Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer

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Abstract

Triple-negative breast cancer (TNBC) is a subset of breast cancer with aggressive characteristics and few therapeutic options. The lack of an appropriate therapeutic target is a challenging issue in treating TNBC. Although a high level expression of epidermal growth factor receptor (EGFR) has been associated with a poor prognosis among patients with TNBC, targeted anti-EGFR therapies have demonstrated limited efficacy for TNBC treatment in both clinical and preclinical settings. However, with the advantage of a number of clinically approved EGFR inhibitors (EGFRis), combination strategies have been explored as a promising approach to overcome the intrinsic resistance of TNBC to EGFRis. In this review, we analyzed the literature on the combination of EGFRis with other molecularly targeted therapeutics or conventional chemotherapeutics to understand the current knowledge and to provide potential therapeutic options for TNBC treatment.

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The biology, function, and biomedical applications of exosomes

Raghu Kalluri, Valerie LeBleu (2020)

The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics.

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Comprehensive molecular portraits of human breast tumors

Nikolaus Schultz (2013)

Summary We analyzed primary breast cancers by genomic DNA copy number arrays, DNA methylation, exome sequencing, mRNA arrays, microRNA sequencing and reverse phase protein arrays. Our ability to integrate information across platforms provided key insights into previously-defined gene expression subtypes and demonstrated the existence of four main breast cancer classes when combining data from five platforms, each of which shows significant molecular heterogeneity. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at > 10% incidence across all breast cancers; however, there were numerous subtype-associated and novel gene mutations including the enrichment of specific mutations in GATA3, PIK3CA and MAP3K1 with the Luminal A subtype. We identified two novel protein expression-defined subgroups, possibly contributed by stromal/microenvironmental elements, and integrated analyses identified specific signaling pathways dominant in each molecular subtype including a HER2/p-HER2/HER1/p-HER1 signature within the HER2-Enriched expression subtype. Comparison of Basal-like breast tumors with high-grade Serous Ovarian tumors showed many molecular commonalities, suggesting a related etiology and similar therapeutic opportunities. The biologic finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biologic subtypes of breast cancer.

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Autophagy: renovation of cells and tissues.

Noboru Mizushima, Masaaki Komatsu (2011)

Autophagy is the major intracellular degradation system by which cytoplasmic materials are delivered to and degraded in the lysosome. However, the purpose of autophagy is not the simple elimination of materials, but instead, autophagy serves as a dynamic recycling system that produces new building blocks and energy for cellular renovation and homeostasis. Here we provide a multidisciplinary review of our current understanding of autophagy's role in metabolic adaptation, intracellular quality control, and renovation during development and differentiation. We also explore how recent mouse models in combination with advances in human genetics are providing key insights into how the impairment or activation of autophagy contributes to pathogenesis of diverse diseases, from neurodegenerative diseases such as Parkinson disease to inflammatory disorders such as Crohn disease. Copyright © 2011 Elsevier Inc. All rights reserved.

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Author and article information

Contributors

Massimiliano Tognolini: Role: Academic Editor

Journal

Journal ID (nlm-ta): Pharmaceuticals (Basel)

Journal ID (iso-abbrev): Pharmaceuticals (Basel)

Journal ID (publisher-id): pharmaceuticals

Title: Pharmaceuticals

Publisher: MDPI

ISSN (Electronic): 1424-8247

Publication date (Electronic): 18 June 2021

Publication date Collection: June 2021

Volume: 14

Issue: 6

Electronic Location Identifier: 589

Affiliations

[1 ]Department of Biochemistry, College of Medicine, Dankook University, Cheonan 31116, Chungcheongnam-do, Korea; kisuhezu@ 123456gmail.com

[2 ]Graduate School of Convergence Medical Science, Dankook University, Cheonan 3116, Chungcheongnam-do, Korea

[3 ]Department of Nanobiomedical Science, Dankook University, Cheonan 31116, Chungcheongnam-do, Korea; dragon101@ 123456gmail.com (Y.W.Y.); jeonghee.cho@ 123456dankook.ac.kr (J.C.)

Author notes

[* ]Correspondence: jeongsp@ 123456dankook.ac.kr (J.-S.P.); seongys@ 123456dankook.ac.kr (Y.-S.S.); Tel.: +82-41-550-3876 (J.-S.P.); +82-41-550-3875 (Y.-S.S.)

[†]

These authors contributed equally to this work.

Author information

Kyu Sic You https://orcid.org/0000-0002-2117-5219

Yong Weon Yi https://orcid.org/0000-0001-6895-0465

Jeonghee Cho https://orcid.org/0000-0003-4422-6266

Yeon-Sun Seong https://orcid.org/0000-0002-4743-8048

Article

Publisher ID: pharmaceuticals-14-00589

DOI: 10.3390/ph14060589

PMC ID: 8233743

PubMed ID: 34207383

SO-VID: 20abb154-ed73-489c-bae5-47cbbb033921

License:

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://creativecommons.org/licenses/by/4.0/).

Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer

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Most cited references 649

The biology, function, and biomedical applications of exosomes

Comprehensive molecular portraits of human breast tumors

Autophagy: renovation of cells and tissues.

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